Medicine and Health Sciences Commons^™

Examining The Oxidative Stress Effects In Rats Exposed To 2-Aminoanthracene In Utero And High Fat Diet Three Months After, Brianna A. Lanoix

Honors College Theses

Polycyclic aromatic hydrocarbons are organic compounds that are created synthetically or found in partially burned oil, gasoline, and coal. 2-aminoanthracene (2AA) is a common example of a PAH and can affect lipid and carbohydrate metabolism and resulting in inflammatory problems and oxidative stress. The objective of the research project is to investigate oxidative stress in relation to diabetes in rats exposed to 2AA in utero and a high fat diet later in life. Pregnant dams were separated into treatment groups based on their dosages of 2AA; 0 mg/kg (control), 50 mg/kg (low), 100 mg/kg (high). During the gestation -postpartum period, …

Roles Of Oxidative Stress And Dna Methylation In Cigarette Smoking-Induced Accelerated Acute Myeloid Leukemia Progression, Mary Figueroa

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) is a commonly diagnosed cancer in smokers. When current or former smokers have AML, they have worse survival compared to never smoking patients. This has been observed clinically for decades, but then it is unknown how smoking leads to worsened AML survival. Smoking causes oxidative stress and altered DNA methylation that persists for decades in peripheral blood mononuclear cells, but these changes from smoking have not been evaluated in the context of AML. We hypothesize that smoking-induced molecular changes, including altered DNA methylation associated with poor AML prognosis, promote AML. We developed a novel model to …

Mechanisms Of Dopamine-Induced Methamphetamine Neurotoxicity, Melinda L. Asbury

Theses, Dissertations and Capstones

Methamphetamine (MA) neurotoxicity is particularly evident in the striatum where it causes extensive dopamine (DA) release and results in neurodegeneration. To identify specific signaling pathways and macromolecules involved in postsynaptic DA-induced striatal toxicity we used a SK-N-MC cell model that mimics postsynaptic D1 receptor-expressing striatal neurons. The cells were treated for 6-24 h with 0-50 µM DA. The concentration was chosen to impart physiological relevance to the study as it mirrors [DA] found within the striatum following MA exposure. We show that 25-50 µM DA resulted in protein changes consistent with nitro(oxidative) stress as well as enhanced cleavage of caspase …

A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin

Electronic Theses and Dissertations

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with type 2 diabetes (T2D). Our recently engineered FGF1 partial agonist, carrying triple mutations (FGF1^△HBS) exhibits greatly reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1. This study tests the preventive and therapeutic effects of FGF1^△HBS on NAFLD in db/db T2D and explores potential mechanisms. The results showed that administration of FGF1^△HBS to 2-month-old db/db mice for 2 months constantly lowered blood glucose levels, improved insulin sensitivity, and lowered liver weight, lipid deposition, and …

Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy

Theses, Dissertations and Capstones

Tenofovir (TFV) is a reverse transcriptase inhibitor that is approved by the United States Food and Drug Administration (FDA) to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for once a day dosing and is effective in treatment of both naive and experienced patients. It is administered orally as tenofovir disoproxil fumarate (TDF) and is deesterified in plasma to the active drug TFV. However, renal impairment is associated with its use; TFV can induce decreased glomerular filtration rate (GFR) and free calcitriol, renal failure, and Fanconi Syndrome. The exact mechanism of toxicity currently remains unknown, largely …

Selective Elimination Of Malignant Melanoma Using The Novel Anti-Tumor Agents, Osw-1 And Peitc, Kausar Begam Riaz Ahmed

Dissertations & Theses (Open Access)

Metastatic melanoma is amongst the most refractory of cancers. Drug resistance and lack of therapeutic selectivity are two main challenges to successful melanoma therapy. Herein, we investigated the mechanims of anticancer activity and therapeutic selectivity of two novel agents, 3β, 16β, 17α-trihydroxycholest-5-en-22-one 16-O-[2-O-4-methoxybenzoyl-β-D-xylopyranosyl]- [1→3]-2-O-acetyl-α-l-arabinopyranoside (OSW-1) and β-Phenylethyl Isothiocyanate (PEITC) in melanoma.

OSW-1 inhibited melanoma cell viability at nanomolar concentrations with minimal toxicity to normal melanocytes. Mechanistic studies revealed that OSW-1 suppressed Disialoganglioside 3 Synthase (GD3S) gene expression in melanoma cells, leading to inhibition of gangliosides GD3 and GD2. GD3 is an abundantly expressed melanoma …

Toxicological Effects Of Cerium Oxide Nanoparticle Aggregates On Caenorhabditis Elegans, Steven N. Rogers

Theses, Dissertations and Capstones

Assessing the toxicity and unique reactivity of nanoparticles in biological systems has become an relevant and quickly growing area of environmental toxicology research. The broad use of nanoparticles in industrial and commercial commodities results in exposure of these nano-compounds to the environment, the ecosystems, and humans. While previous data has suggested that cerium oxide (CeO₂) nanoparticles are relatively safe to cultured cells much less is known about the potential toxicity of these materials at the organismal level. In this study we employed transgenic Caenorhabditis elegans (C. elegans) strains to assess the toxicity of CeO₂ nanoparticles under “real-world” …

Secreted Factors From Human Umbilical Cord Blood Cells Protect Oligodendrocytes From Ischemic Insult, Derrick Rowe

USF Tampa Graduate Theses and Dissertations

Oligodendrocytes (OL)s are the dominant cell type in the white matter and are integral for synaptic transmission essential for proper neuronal communication between brain areas. Previous studies have shown that intravenous administration of the mononuclear fraction of human umbilical cord blood (HUCB) cells in rat models of stroke reduced white matter injury, gray matter injury and behavioral deficits. Yet the mechanisms used by HUCB cells remain unknown in ischemic injury. These studies will investigate both in vitro and in vivo approaches to elucidate this mechanism in OLs. When mature primary OLs were coincubated with HUCB cells, HUCB cells secreted soluble …