Reducing Placental Oxidative Stress In A Rat Model Preeclampsia Using Vegfr2 Nanoparticles, Sophia Ganios

Williams Honors College, Honors Research Projects

Preeclampsia is a complication of pregnancy, where the placenta lacks sufficient blood flow due to abnormal formation of the vascular endothelial cells. This results in hypertension and increased reactive oxygen species, causing oxidative stress. The VEGF (vascular endothelial growth factor) helps develop new growth, so by increasing the receptors VEGFR2 by injection of LTP nanoparticles into the uterine wall of RUPP rats, one can see if there would be improvement in the otherwise reduced uterine pressure pregnant rat. This would be confirmed by the 8-isoprostane test, which measures oxidative stress.

Stromal Vascular Fraction Restores Vasodilatory Function By Reversing Mitochondrial Dysfunction And Oxidative Stress In Aging-Induced Coronary Microvascular Disease., Evan Paul Tracy

Electronic Theses and Dissertations

Background: Coronary Microvascular Disease (CMD) presents in aging post-menopausal women with chronic angina due to microvascular hyperconstriction. The objective was to identify mechanisms of adipose stromal vascular fraction’s (SVF) restorative effects on vasodilation. We hypothesize aging-induced CMD is caused by a) abrogated flow-mediated dilation (FMD) due to loss of nitric oxide signaling and b) ROS-dependent βADR desensitization & internalization, reversible by ameliorating mitochondrial dysfunction and oxidative stress with SVF. Methods: Coronary microvessels were isolated from female rats either young, old, or old with SVF tail-vein injection (OSVF). Pressure myography, RNA-sequencing, immunofluorescence, Western blotting, and morphological analysis were performed to …

Knockdown Of C. Elegans Nad Kinases Nadk-1 Or Nadk-2 Induces An Antioxidant Response Without Affecting Lifespan, Henry Gong

Electronic Theses and Dissertations

Nearly all multicellular organisms show changes in redox balance with aging leading to oxidative damage of macromolecules. This study investigated the role of the [NADP⁺]/[NADPH] redox couple in aging. This redox couple plays an important role in maintaining tissue redox balance and becomes slightly more oxidized in aged tissues. NADPH is a major source of reducing equivalents for enzymes that detoxify hydrogen peroxide. However, catalase detoxifies hydrogen peroxide independently of NADPH. But catalase is absent from mitochondria, a major source of hydrogen peroxide, where instead glutathione plays the major role in hydrogen peroxide detoxification in an NADPH-dependent manner. …

Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos

Graduate Theses, Dissertations, and Problem Reports

Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …

Role Of Limonene In An Experimental Model Of Rotenone Induced Parkinson’S Disease, Lujain Mohamad Bader Eddin

Theses

Parkinson's disease (PD) is one of the prevalent neurodegenerative diseases in elderly population. The symptoms of PD often begin with motor and cognitive impairment that are attributed to the dopaminergic neurons degeneration. Rotenone (ROT) is a naturally derived pesticide that is used in agriculture to control pests. It is a neurotoxin well-established for use in resembling PD symptoms in research. Limonene (LMN) is a plant derived monoterpene extracted from citrus peel with a wide range of therapeutic effects. Due to the shortage in available therapeutic agents that can cure or halt the progressive degeneration of PD, the main aim of …

Therapeutic Potential Of A Ketogenic Diet In The Treatment Of Major Depressive Disorder, Jordan A. Murrin

Masters Theses, 2020-current

Major depressive disorder (MDD) is the second most common mental health condition and a leading cause of disability in the world. It is theorized that MDD develops from a combination of biological, psychological, and social stressors. The condition is typically treated using pharmaceuticals and psychotherapy. However, not all individuals with MDD have access to or choose to use these treatments, or may prefer to incorporate therapeutic lifestyle changes such as exercise, sleep, and healthy eating. Even with treatment, MDD can alter brain structure and function, leading to the development of comorbid mental health and chronic metabolic conditions like obesity, cardiovascular …

Effect Of N-Acetyl-L-Cysteine Prevention Or Intervention On Diet Induced Beta Cell Compensation And Dysfunction, Madison Wallace

Electronic Thesis and Dissertation Repository

Type 2 diabetes mellitus (T2DM) progression increases oxidative stress which contributes to beta cell compensation and eventual dysfunction. To investigate the role of antioxidant N-acetyl-L-cysteine (NAC) on beta cell function and pancreatic stellate cell activation (aSMA⁺) during early and late stages of compensation, NAC was used for preventative (p) and intervention (i) treatments in C57BL/6N mice fed a 60% kcal high-fat diet (HFD) for 8 or 22 weeks. Significantly improved glucose tolerance was observed at 22 weeks following pNAC treatment in HFD mice. Although 22-week HFD mice displayed hyperinsulinemia, beta cell hypertrophy, decreased beta cell PDX-1 nuclear localization, …

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …

Mechanistic Study Of Diatrizoic Acid Induced Proximal Tubule Cytotoxicity, Dakota Blake Ward

Theses, Dissertations and Capstones

Radiocontrast media (RCM) are necessary for many diagnostic procedures such as arteriography, percutaneous coronary intervention (PCI), and computed tomography. Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-associated kidney damage accounting for 10-25% of cases worldwide. The mechanisms of contrast-induced renal impairment are not entirely known, but diminished renal hemodynamics, inflammatory responses, and direct cytotoxicity have been hypothesized. The purpose of this study was to investigate the mechanisms of direct cytotoxicity observed in HK-2 cells following treatment with diatrizoic acid (DA) and to determine the source of this damage. Mitochondrial function, endoplasmic reticulum (ER) stress, oxidative …

Determination Of The Role Of Smu_833 In The Fitness And Virulence Of Cariogenic Streptococcus Mutans, Katherine Lynn Rainey

All ETDs from UAB

Dental caries, commonly known as tooth decay, is the most common infectious disease worldwide. The main etiological agent of dental caries is Streptococcus mutans which can readily form a biofilm on the surface of teeth and produce acids through the metabolism of dietary sugars, which is largely responsible for the demineralization and subsequent destruction of tooth enamel. In addition, S. mutans synthesizes extracellular glucosyltransferases (Gtfs) capable of breaking apart dietary sucrose and polymerizing the glucose subunits into the sticky glucan matrix of the biofilm, imperative for the formation of robust, three-dimensional biofilms. Currently used caries therapies are not species-specific and …

Chronic Low Intensity Continuous And Interval Training Prevent Heart Failure-Related Coronary Artery Stiffness, An Ouyang

Theses and Dissertations--Kinesiology and Health Promotion

Heart failure (HF) induced by aortic pressure over-load is associated with increased coronary artery stiffness. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness. However, the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. The present study hypothesized both chronic continuous and interval exercise training would prevent coronary artery stiffness associated with inhibition of PVAT secreted AGE. Yucatan mininature swine were divided into four groups: control-sedentary (CON), aortic-banded sedentary heart failure (HF), aortic-banded HF continuous exercise trained (HF+CONT), and aortic-banded HF interval exercise trained …

Investigating The Role Of Endogenous Atf4 Upregulation On Neuronal Glutathione Level, Fatemeh Mirshafiei

Electronic Thesis and Dissertation Repository

ATF4 is a transcription factor that is activated in response to integrated stress response (ISR). In neurons specifically, ATF4 has been suggested to act as a pro-apoptotic transcription factor. The expression of ATF4, as well as its downstream gene targets have been implicated in both in vivo and in vitro models of Alzheimer’s and Parkinson’s Disease. However, the mechanism by which ATF4 promotes cell death remains unclear. It was previously shown that overexpression of ATF4 in primary cortical neurons caused a reduction in glutathione levels, resulting in oxidative stress-induced cell death. The aim of this project was to investigate whether …

Role Of Oxidized Extracellular Vesicles As Early Biomarkers And Inflammatory Mediators In Chemotherapy-Induced Normal Tissue Injury, Chontida Yarana

Theses and Dissertations--Toxicology and Cancer Biology

Significant advances in the efficacy of cancer therapy have been accompanied by an escalation of side effects that result from therapy-induced injury to normal tissues. Patients with high grade cancer or metastasis are often treated with chemotherapy, 50% of which are associated with reactive oxygen species generation and cellular oxidative stress. Heart is the normal tissue most susceptible to chemotherapy-induced oxidative stress and heart disease is the most common leading cause of death in cancer survivors. However, early and sensitive biomarkers to identify heart disease are still lacking. Extracellular vesicles (EVs) are released from cells during oxidative stress and send …

Short-Term Bilateral Adrenalectomy: Biochemical And Morphological Alterations In The Rat Hippocampus, Ahlam Said Abi Issa

Theses

Several studies showed the effects of glucocorticoid hormones on the hippocampus. It has been reported that the chronic administration of high dose glucocorticoids (GC) results in the degeneration of pyramidal neurons. However, bilateral adrenalectomy has been shown to damage the hippocampal neurons. Although the effects of long-term adrenalectomy have been studied extensively, there are few publications on the effects of short-term bilateral adrenalectomy (ADX). We aimed to investigate the effects of ADX on levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interkeukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); levels of growth factors, response of microglia and astrocytes to neuronal death, and oxidative …

The Potential Role Of Oxidative Stress In Reduced Uterine Perfusion Pressure Vascular Reactivity, Abigail J. Gindlesberger

Williams Honors College, Honors Research Projects

Preeclampsia is a hypertensive disease of pregnant women that is known to cause detrimental physiological complications to both the mother and fetus. The hypertension hypothesized to result from endothelial dysfunction may be improved therapeutically by increasing Vascular Endothelial Growth Factor ligand concentration and it’s Vascular Endothelial Growth Factor Receptor 2 (VEGF and VEGFR2). Together, this receptor pathway may help overall vasodilation of key blood vessels linking the mother and fetal placental unit, allowing for increased clinical pathologies of both. Previous studies have also linked increased reactive oxygen species (ROS) production in preeclamptic pregnancies to the damaged endothelial tissues of the …

Effect Of Genipin On Cisplatin- Induced Nephrotoxicity, Eglal Orner Mahgoub

Theses

Cisplatin (CSP) is a potent and widely used chemotherapeutic agent. However, clinical efficacy of CSP is compromised due to the elicitation of nephrotoxicity and ototoxicity. In this study, I have investigated the nephroprotective effects of a phytochemical – genipin (GP) isolated from gardenia flower (Gardenia jasminoides), on a murine model of cisplatin-induced nephropathy. CSP-induced renal tissue injury was characterized by elevated levels of serum blood urea nitrogen (BUN), creatinine (Cr) and cystatin-C. In addition, levels of kidney injury molecule-1 (KIM-1) were increased in the renal tissues of CSP administered animals. CSP also induced renal oxidative stress, evidenced by increased NADPH …

Novel Role Of Cd47 In Obesity-Associated Metabolic Dysfunctions, Heather L. Norman-Burgdolf

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity and its associated comorbidities are of global concern. These complications are largely driven by perturbations in energy homeostasis, inflammation, and oxidative stress within metabolic tissues. Although these underlying pathways have been established, molecular mechanisms augmenting metabolic dysfunction have not been fully defined. CD47, a ubiquitously expressed cell membrane receptor, has been previously implicated in the development of inflammation and oxidative stress in a number of disease conditions. Previous work from our lab and others has confirmed that the most potent ligand of CD47, TSP1, plays a critical role in facilitating inflammation and metabolic dysfunction in diet-induced obesity. Whether these …

Pathophysiologic Mechanisms Of Immune-Mediated Drug Hypersensitivity Reactions To Sulfonamides, Elham A. Sultan

Electronic Thesis and Dissertation Repository

As sulfonamide hypersensitivity reactions are serious clinical problem, it is necessary to determine which patients tolerate therapy and which patients are at risk. Although the exact pathogenesis of these reactions remains unclear, the imbalance in the production and detoxification of reactive sulfamethoxazole (SMX) metabolites appears to be important in the propagation of these reactions. It is known that these reactive metabolites can cause lymphocytes toxicity and produce reactive oxygen species (ROS) which can damage proteins, lipids, and DNA. The hypothesis of this research is that there are differences in cytotoxicity and expression of oxidative stress to reactive SMX metabolites in …

Nicotinamide Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn

Electronic Thesis and Dissertation Repository

The ability of vascular cells to withstand oxidative insults is critical to vascular health. NAD⁺, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD⁺ stores and fuel resistance to oxidative stress. I established that oxidative-stress insult on vascular cells decreased NAD⁺ levels, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition abolished PAR-chain formation and preserved NAD⁺ levels, establishing PARP in NAD⁺ consumption in this …

Mechanisms Of Atf4-Mediated Neuronal Apoptosis, Patrick Swan

Electronic Thesis and Dissertation Repository

Abstract to be provided

Protective Effect Of Modified Human Fibroblast Growth Factor On Diabetic Nephropathy, Ana M. Pena Diaz

Electronic Thesis and Dissertation Repository

Oxidative stress is a key mechanism causing Diabetic Nephropathy (DN). Acidic fibroblast growth factor (aFGF) is known to confer protection from oxidative stress. However, it also has significant angiogenic activity. Hence, we have generated a mutated human acidic FGF (maFGF), with intact antioxidant properties but devoid of angiogenic activities. Recent evidence shows that maFGF treatment prevented diabetic cardiomyopathy and further in vitro studies suggest that this prevention is mediated by suppression of cardiac oxidative stress, hypertrophy and fibrosis. We hypothesized that maFGF treatment has a protective effect in DN.

We show that maFGF treatment did not affect body weight and …

Metabolic And Oxidative Regulation Of Neuronal Autophagy And Survival, Matthew Dodson

All ETDs from UAB

Neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease are all characterized by metabolic dysfunction, increased oxidative damage to proteins and organelles, formation of proteinaceous inclusions, decreased autophagic and proteasomal function, and eventual neuronal and glial cell death. While our understanding of the mechanisms that underlie many of these pathologies is constantly growing, their exact cause, onset, interplay and progression still remain unclear. The gap between the description of disease pathologies and understanding the fundamental mechanisms of disease pathogenesis, progression and potential therapeutics to mitigate disease progression is still large. Based on the observation that altered glucose utilization, …

Bioenergetics As A Biomarker Of Health And Disease, Philip Kramer

All ETDs from UAB

The increasing prevalence of metabolic syndrome, diabetes, atherosclerosis, and many other diseases only recently associated with aberrant metabolism, have led to a de-mand for clinical assays to determine a patient’s mitochondrial health. With the rapidly growing interest in personalized medicine, such an assay would ideally be able to capture the metabolic changes associated with oxidative stress, inflammation, and therapy of a patient in a swift and non-invasive manner. Short of tissue biopsies, this burgeoning field of Translational Bioenergetics has had minimal success in obtaining sufficient human cells and the means to assess them both accurately and swiftly. The purpose of …

Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi

All ETDs from UAB

The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …

Regulation Of The High-Affinity Choline Transporter Activity And Trafficking In Alzheimer’S Disease-Related Pathological Conditions, Leah K. Cuddy

Electronic Thesis and Dissertation Repository

Cholinergic neurons play a key role in cognitive processes through the action of the neurotransmitter acetylcholine (ACh). Dysfunction of these neurons occurs in several neurodegenerative disorders, including Alzheimer’s disease (AD). The high-affinity choline transporter CHT recycles choline back into synaptic terminals, which is the rate-limiting step to ACh production. CHT proteins traffic between the cell surface and subcellular organelles in a constitutive manner, which maintains plasma membrane transporter levels, thereby regulating CHT activity and maintaining cholinergic transmission. Pathological conditions associated with AD may alter CHT function in a manner that reduces choline uptake activity and impairs cholinergic neurotransmission. Thus, my …

Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara

Dissertations & Theses (Open Access)

Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia diagnosed in Western countries and is characterized by clonal expansion of B cells. The clinical course of CLL is diverse and nearly 50% of patients present with chromosomal abnormalities. Deletion of the short arm on chromosome 17 (del17p) occurs in 5-7% of cases and presents with the shortest median survival time and often respond poorly to therapy. The tumor suppressor gene, TP53 is located on this region and it is well established that the p53 protein regulates multiple functions including: mitochondria biogenesis, response to DNA damage and redox balance. …

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Neuroprotective Effects Of Gamma-Glutamylcysteine Ethyl Ester On An In Vivo Moderate Traumatic Brain Injury-Mediated Model And In Vitro In Cortical Astrocytes And Neurons, Jooyoung Cho

Online Theses and Dissertations

Neurodegeneration is the loss of neuronal structures or functions, while neuroprotection is the delay or prevention of neurodegeneration. In traumatic brain injury (TBI), neurodegeneration can occur as the result of oxidative stress, the imbalance of oxidants and antioxidants levels; therefore, antioxidant approaches can be effective therapeutic methods for neuroprotection by attenuating oxidative stress. Glutathione (GSH), a naturally occurring antioxidant, plays an important role in the maintenance of intracellular redox homeostasis by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this thesis, we attempted to evaluate the abilities of a GSH precursor, gamma-glutamylcysteine ethyl ester (GCEE), to prevent …

Effect Of Procedural Pain On Purines, Mda And Allantoin In Premature Infants, Megan Sue Holden

Loma Linda University Electronic Theses, Dissertations & Projects

Identifying and measuring the biochemical effects of procedural pain in infants is a continuing challenge for clinicians. To address this issue we evaluated the relationship between procedural pain, ATP utilization (hypoxanthine and uric acid), and oxidative stress (MDA and allantoin) in premature infants. Through these studies we found that 1) a single heel-lance significantly increases plasma uric acid in rabbit kits, 2) tape removal increases MDA and prevents a decrease in uric acid in the plasma of premature infants, and 3) a single dose of oral sucrose before a heel-lance is sufficient to significantly increase plasma markers of ATP utilization …

Oxidative Stress For An Acute Bout Of Bikram Yoga In Healthy, Trained Adults, Kimberly Anne Trocio

UNLV Theses, Dissertations, Professional Papers, and Capstones

BACKGROUND:Generation of free radicals resulting in oxidative damage has been linked to cellular damage, aging, and human disease. Many studies have reported that physical exercise can contribute to oxidative stress. Further, exercise in a hyperthermic environment can promote additional oxidative stress. It is important to consider that practices in yoga may be beneficial in reducing oxidative stress according to some studies. The compound effects of exercise and hyperthermic exposure are experienced in the practice of Bikram yoga, the original "hot" yoga. Because Bikram yoga and other hot exercise classes are an increasingly growing fitness trend, it is necessary to investigate …