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Articles 1 - 30 of 45
Full-Text Articles in Toxicology
Characterizing Hexavalent Chromium Neurotoxicity Across Laboratory Models., Samuel Thomas Vielee
Characterizing Hexavalent Chromium Neurotoxicity Across Laboratory Models., Samuel Thomas Vielee
Electronic Theses and Dissertations
Hexavalent chromium [Cr(VI)] is a ubiquitous environmental pollutant and potent toxicant. Exposure to Cr(VI) in drinking water is primarily associated with cancers, inflammation, and hepatotoxicity; however, recent studies have identified Cr(VI) as a neurotoxicant in rodent and cell culture models. The literature suggest chromium accumulates in the brain, induces widespread neurodegeneration, and alters rodent behaviors. Despite these data, we lack a detailed and consistent assessments of Cr(VI) neurotoxicity across models, and interactions between aging and Cr(VI) neurotoxicity are not reported in the literature. In this dissertation, we characterize Cr(VI) neurotoxicity across 3 laboratory models: Sprague-Dawley rats, Caenorhabditis elegans, and …
Exposure To Pm2.5 And Aging., Daniel Chris Gomes
Exposure To Pm2.5 And Aging., Daniel Chris Gomes
Electronic Theses and Dissertations
Inhalation of fine airborne particulate matter (PM2.5) is an environmental risk factor for numerous health disorders, including cardiovascular diseases (CVD). While several studies have shown that PM2.5 exposure can induce oxidative stress, DNA damage, and inflammation, the underlying mechanisms that translate these effects into systemic pathology remain poorly understood. Some recent studies have shown that PM2.5 exposure can lead to telomere shortening in leukocytes, but the generality of this outcome and contribution to endothelial dysfunction has not yet been fully explored. We hypothesized that PM2.5inhalation accelerates cellular aging and senescence in both circulating peripheral …
Translation Of The Carcinogenic Dna Breakage-Repair Inhibition Mechanism For Hexavalent Chromium To Its Key Targets: Lung Epithelial Cells, Lung Tissue And Impacts On The Genome., Idoia Meaza Isusi
Electronic Theses and Dissertations
Lung cancer is the leading cause of cancer death worldwide. Hexavalent chromium [Cr(VI)] is a human lung carcinogen with widespread occupational and environmental exposure. Despite the known health risks, how Cr(VI) causes lung cancer remains unclear. This dissertation investigates the mechanisms of Cr(VI)-induced carcinogenesis. Cr(VI) causes DNA damage, specifically DNA double strand breaks, and inhibits homologous recombination repair, a high-fidelity repair pathway. Unrepaired DNA double strand breaks or those repaired through error-prone pathways, progress to chromosomal damage, and chromosome instability. The latter is a common characteristic of Cr(VI)-exposed cells, and a hallmark of lung cancer. Although the mechanism of Cr(VI)-induced …
Mechanisms Of Particulate Hexavalent Chromium-Induced Inhibition Of Homologous Recombination Repair: Targeting The Bcdx2 Complex Considered Through A One Health Perspective., Aggie W. Brownell
Electronic Theses and Dissertations
Lung cancer remains the leading cause of cancer death, often linked to smoking. However, smoking alone does not account for all cases. Exposure to environmental metals like hexavalent chromium [Cr(VI)] also contributes to lung cancer. Cr(VI) causes lung cancer by inducing chromosome instability (CIN), an early hallmark of its carcinogenic mechanism. While it has been established that Cr(VI) induces chromosome instability, the precise mechanisms underlying the chromosome instability are poorly understood. This dissertation investigates the mechanisms of carcinogenesis associated with zinc chromate, a particularly potent particulate form of hexavalent chromium. Studies show Cr(VI) induces DNA double-strand breaks and impairs the …
Using A Toxic Aging Coin To Assess Hexavalent Chromium-Induced Neurotoxicity., Samuel Thomas Vielee
Using A Toxic Aging Coin To Assess Hexavalent Chromium-Induced Neurotoxicity., Samuel Thomas Vielee
Electronic Theses and Dissertations
We are facing an aging crisis, with 20% of the U.S. population projected to be geriatric (65+) by 2030 and live another 40+ years. Age-related diseases accompany a growing geriatric population, emphasizing the need to understand their etiology. Environmental pollutants compound this crisis by: 1) geriatrics are more susceptible, exacerbating age-related diseases and comorbidities, and 2) they accelerate biological aging, inducing age-related diseases at younger ages. We address this crisis using a ‘toxic aging coin’ approach; heads examines how age impacts toxicity, tails examines how chemicals accelerate aging. This thesis applies the heads side for Cr(VI)-induced neurotoxicity across ages. We …
The Impact Of Environmental Pollutants On Alcohol-Associated Liver Disease Pathogenesis., Tyler Charles Gripshover
The Impact Of Environmental Pollutants On Alcohol-Associated Liver Disease Pathogenesis., Tyler Charles Gripshover
Electronic Theses and Dissertations
Steatotic liver disease is brought upon by differing etiologies and its global prevalence is expected to keep increasing over the next several decades. Particularly, alcohol-associated liver disease (ALD) manifests from excessive alcohol consumption where the liver retains lipids and progresses with metabolic dysfunction. Previous studies have demonstrated that environmental pollutants, polychlorinated biphenyls (PCBs) promote metabolic dysfunction associated steatotic liver disease (MASLD), in diet-induced obesity models. However, it is unknown if environmental pollutants may also promote ALD pathogenesis. Thus, this dissertation focuses on characterizing the effects of PCB126 in a rodent ALD model followed by multiple ‘Omics approaches to identify mechanisms …
Epitranscriptomic Regulation In Breast Cancer And Pcb-Induced Liver Disease., Belinda Petri
Epitranscriptomic Regulation In Breast Cancer And Pcb-Induced Liver Disease., Belinda Petri
Electronic Theses and Dissertations
Post-transcriptional RNA modifications including N6-methyladenosine (m6A) regulate mRNA stability, splicing, and translation. My research examined m6A in two disease models: breast cancer (BCa) and non-alcoholic fatty liver disease (NAFLD). Acquired resistance to endocrine therapies (ET) develops in approximately 20% of BCa patients with estrogen receptor α positive (ER+) tumors following treatment. The mechanisms by which tumor cells evade ET are not completely understood. Using a cell line model, we investigated the role of an m6A reader protein, HNRNPA2B1 (A2B1) that is upregulated in ET-resistant ER+ BCa cells. Stable overexpression of A2B1 in ET-sensitive MCF-7 cells (MCF-7-A2B1), results in ET resistance, …
The Role Of E-Liquid Constituents In E-Cigarette-Induced Cardiac Arrhythmia And Autonomic Imbalance., Cory Kucera
The Role Of E-Liquid Constituents In E-Cigarette-Induced Cardiac Arrhythmia And Autonomic Imbalance., Cory Kucera
Electronic Theses and Dissertations
Introduction. Accumulating evidence indicates that exposure to electronic cigarettes (e-cigs) promotes sympathetic dominance and electrophysiologic instability in the heart, potentially culminating in arrhythmogenesis. E-liquids contain various formulations of nicotine and flavorings, but the effects of specific e-liquid constituents and their concentrations on e-cig-induced autonomic imbalance and electrical dysfunction are unresolved. To that end, we tested the hypothesis that e-cigs modify cardiac autonomic balance and ventricular arrhythmogenesis in mice dependent on e-liquid constituent type and concentration. Methods. Using a crossover design and a serial exposure regimen, ECG-telemetered male C57BL/6J mice underwent whole-body exposure to e-cig aerosols generated from e-liquids containing different …
Effects Of Environmental Pollutants On Liver Disease: Role Of The Gut-Liver Axis., Ngozi Victoria Adiele
Effects Of Environmental Pollutants On Liver Disease: Role Of The Gut-Liver Axis., Ngozi Victoria Adiele
Electronic Theses and Dissertations
Polychlorinated biphenyls (PCBs) and polystyrene (PS) microplastics are environmental pollutants associated with various diseases including toxicant associated fatty liver disease (TAFLD). Previously, exposure to Aroclor 1260 (a PCB mixture) has been shown to exacerbate TAFLD, partly through Aroclor 1260 induced gut dysbiosis. Studies has also demonstrated that PS exposure alters gut microbiome composition and induced obesity. However, the effects of Aroclor 1260 on the gut and the effects of PS on the liver are still understudied. Therefore, we hypothesize that environmental pollutants will disrupt the gut-liver axis through changes in gut and its microbiome as well as changes in liver …
The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall
The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall
Electronic Theses and Dissertations
Volatile organic compounds (VOCs) are a group of pervasive air pollutants that are released into the atmosphere from both anthropogenic and environmental sources. Recent epidemiological studies suggest that exposure to various VOCs is associated with an increased risk of cardiovascular disease. However, the relationship between VOCs and cardiovascular disease is not well-studied. Using animal models and three select VOCs, benzene, xylene, and trichloroethylene, we studied the effects of VOCs on endothelial injury and benzene-induced atherogenesis. We found that exposure to benzene and xylene increased circulating endothelial microparticles, depleted progenitor cells, and increased platelet activation. Following the exposure to the representative …
Investigation Of Human N-Acetyltransferases (Nat1 And Nat2) Genetic Polymorphisms In Susceptibility To Aromatic Amine And Alkylaniline Genotoxicity., Mariam Habil
Electronic Theses and Dissertations
Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT1 and NAT2 genotypes. We hypothesize that different NATs alleles will impact levels of N-acetylation, HPRT mutations, DNA damage and oxidative stress induced by carcinogens. NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4, NAT1*14B, NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of benzidine, β-naphthylamine (BNA), and 4, 4’-methylene bis (2-chloroaniline) (MOCA) as aromatic amines and 3,4-dimethylaniline (3,4-DMA) as one of alkylanilines and their associated toxicity. Our …
Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams
Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams
Electronic Theses and Dissertations
Hexavalent Chromium [Cr(VI)] is a known human lung carcinogen and general health hazard. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the major theory in its carcinogenic mechanism. Homologous recombination (HR) repair is a DNA repair pathway that prevents CIN by repairing DNA double-strand breaks. RAD51, a key mediator protein of HR repair, along with the RAD51 paralogs (RAD51B, C, D, XRCC2, and 3) are required for HR repair. During HR, RAD51 loads and forms a helical nucleoprotein filament structure to promote DNA strand exchange and stimulate pairing activity of DNA. Cr(VI) exposures have been shown …
Characterizing The Role Of Macrophages In Cisplatin-Induced Kidney Injury And Progression To Chronic Kidney Disease., Sophia M. Sears
Characterizing The Role Of Macrophages In Cisplatin-Induced Kidney Injury And Progression To Chronic Kidney Disease., Sophia M. Sears
Electronic Theses and Dissertations
Cisplatin is a commonly used chemotherapeutic for treatment of many solid-organ cancers. Unfortunately, 30% of patients treated with cisplatin develop acute kidney injury (AKI), and even patients who do not develop AKI are at risk for long term declines in kidney function and development of chronic kidney disease (CKD). While traditional rodent toxicity studies have utilized a single, lethal dose of cisplatin, new models of cisplatin-induced kidney injury have revealed that repeated, low doses of cisplatin lead to development of kidney fibrosis. This model can be used to examine AKI-to-CKD transition processes. C57BL/6 mice are one of the most used …
Translating Particulate Hexavalent Chomium-Induced Chromosome Instability, Loss Of Homologous Recombination Repair And Targeting Of Rad51 From Human Lung Fibroblasts To Human Bronchial Epithelial Cells., Idoia Meaza Isusi
Electronic Theses and Dissertations
Particulate hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen. RAD51, a key protein in homologous recombination repair pathway, is inhibited after prolonged exposure to Cr(VI), leading to an increase in chromosome instability after prolonged exposures in human lung fibroblasts. chromosome instability is the proposed driver of Cr(VI) carcinogenesis. Since tumors from chromate workers develop from epithelial cells, we sought to translate these findings from human bronchial fibroblasts to human bronchial epithelial cells. We hypothesized Cr(VI) inhibits RAD51 after prolonged exposure leading to an increase in chromosome instability in human bronchial epithelial cells (BEP2D). We characterized the cytotoxicity and measured …
Investigating The Effects Of Perfluorooctanoic Sulfonate (Pfos) And Ethanol On Fatty Liver Disease Using A Modified Niaaa Model., Tyler Charles Gripshover
Investigating The Effects Of Perfluorooctanoic Sulfonate (Pfos) And Ethanol On Fatty Liver Disease Using A Modified Niaaa Model., Tyler Charles Gripshover
Electronic Theses and Dissertations
Perfluoroalkyl Substances (PFAS) are a family of man-made, surfactant-like compounds that are a major environmental contaminant. A multitude of studies have indicated that PFAS are able to induce fatty liver disease and modulate lipid metabolism. However, the distinct mechanism of PFAS influence on the liver and metabolism disruption remains to be elucidated. On the other hand, it is well documented that alcohol consumption has various adverse health impacts including fatty liver disease and subsequent progression to more adverse liver states. To date, there are no published studies on whether PFAS and alcohol can jointly exacerbate fatty liver progression or interact …
Assessing The Role Of Chronic Arsenite Exposure In Disrupting The Egfr Signaling Axis., Christine Kim
Assessing The Role Of Chronic Arsenite Exposure In Disrupting The Egfr Signaling Axis., Christine Kim
Electronic Theses and Dissertations
Chronic arsenic exposure is a risk factor for the development of pulmonary diseases, including lung cancer, but the exact mechanism is not yet fully understood. Many previous studies have relied on acute arsenic exposure (i.e. 1-10 uM arsenic for 24 hours) to study arsenic toxicological effects. However, acute exposure does not reflect the levels or duration of arsenic associated with environmental exposure, or drinking of contaminated well water. This dissertation differentiates the effects of acute versus chronic arsenic exposures on the EGFR signaling axis and suggests possible mechanisms for chronic arsenic-induced pulmonary diseases. The EGFR is a receptor tyrosine kinase …
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
Electronic Theses and Dissertations
Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …
Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson
Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson
Electronic Theses and Dissertations
Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …
The Cardiovascular Effects Of Tobacco Product-Derived Aldehydes: Contribution Of Transient Receptor Potential Ankyrin-1., Lexiao Jin
Electronic Theses and Dissertations
Cardiovascular diseases (CVD) are the leading cause of death in most countries and are significant health and financial burden worldwide. Smoking contributes to more than 480,000 premature deaths annually -- accounting for one of every five deaths in the United States each year. Numerous studies have shown that smoking increases the risk of factors including endothelial dysfunction, thrombosis, and atherosclerosis, which may lead to an incidence of myocardial infarction, coronary artery disease, and stroke. Electronic cigarettes (e-cigarettes) are a new kind of tobacco product, and some studies show that e-cigarettes also could induce CVD since both e-cigarettes and conventional tobacco …
Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch
Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch
Electronic Theses and Dissertations
Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …
Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li
Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li
Electronic Theses and Dissertations
Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …
Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud
Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud
Electronic Theses and Dissertations
Background: Periodontal diseases are globally prevalent inflammatory disorders that affect ~47% of U.S adults. Porphyromonas gingivalis (Pg) has been identified as a “keystone” pathogen that disrupts host-microbe homeostasis and contributes to the initiation and progression of periodontitis. Pg associates with oral streptococci in supragingival plaque and this interaction represents a potential target for therapeutic intervention. Previously our group developed a peptide (designated BAR), that potently inhibits Pg/Streptococcus gordonii (Sg) adherence in vitro and Pg virulence in a murine model of periodontitis. While efficacious, BAR (SspB Adherence Region) provided transient inhibition and required higher concentrations of BAR to disrupt established …
A Mechanistic Study Of The Teratogenic Potential Of 4-O-Methylhonokiol (Mh) On Japanese Medaka (Oryzias Latipes), Santu Kumar Singha
A Mechanistic Study Of The Teratogenic Potential Of 4-O-Methylhonokiol (Mh) On Japanese Medaka (Oryzias Latipes), Santu Kumar Singha
Electronic Theses and Dissertations
An additional goal of this project was to characterize the Wnt/β-catenin signaling pathway to unravel the adverse potential of MH on the cardiovascular system (CVS). Our study suggested that MH-mediated cardiovascular injury may be caused due to upregulation of some major components of the Wnt/β-catenin pathway through expression of excessive pro-inflammatory mediators. Moreover MH decreased expression of ErbB3 and NRG-2 suggesting impaired cardiac structure. MH exposure caused a slow heartbeat blood occlusion absence of blood circulation decreased hatching efficiency and increased mortality in medaka embryos in a concentration- and time-dependent manner. MH might cause blood vessel occlusion by increasing the …
The Independent And Combined Effects Of Hypoxia And Tributyltin On The Eastern Oyster, Crassostrea Virginica, Ann Fairly Barnett
The Independent And Combined Effects Of Hypoxia And Tributyltin On The Eastern Oyster, Crassostrea Virginica, Ann Fairly Barnett
Electronic Theses and Dissertations
Oysters are vital to the health of estuarine ecosystems and provide critical ecosystem services, such as water quality improvement, nursery habitat for commercially important fisheries, and shoreline stabilization. Despite their ecological and economic importance, oyster reefs are exposed to many stressors, and oyster populations in Mississippi have declined dramatically in recent years. The present study focuses on the effects of hypoxia and tributyltin (TBT) on the Eastern oyster, Crassostrea virginica. Hypoxic events are increasingly comin coastal ecosystems worldwide, and TBT is a legacy toxicant once used as an antifoulant. The effects of these stressors were assessed on adult oysters deployed …
The Role Of Cyp2a5 In Cadmium-Induced Liver Injury, Julia Salamat
The Role Of Cyp2a5 In Cadmium-Induced Liver Injury, Julia Salamat
Electronic Theses and Dissertations
Cadmium is present in food and groundwater. Tobacco smoking and occupational exposure are also major sources for cadmium. Cadmium is primarily accumulated in liver, a major organ metabolizing exogenous chemicals. Chemical metabolism may cause detoxification, but it can also cause bio-activation resulting in liver damage. Cytochrome P450s (CYP) are major liver metabolism enzymes, and cadmium chloride (CdCl2) can induce CYP2A5 in mice. We examined the effect of CYP2A5 on CdCl2-induced liver injury using CYP2A5-knockout (cyp2a5-/-) mice. The cyp2a5-/- mice and their control WT mice were injected CdCl2 intraperitoneally at 5 mg/kg body weight, respectively, to induce liver injury. …
The Role Of Cathelicidin In The Regulation Of Gut Microbiota And Inflammasome Activation In Alcoholic Liver Disease., Fengyuan Li
The Role Of Cathelicidin In The Regulation Of Gut Microbiota And Inflammasome Activation In Alcoholic Liver Disease., Fengyuan Li
Electronic Theses and Dissertations
Alcoholic liver disease (ALD) is characterized by gut dysbiosis and hepatic and intestinal inflammation. Gut microbiota is critically maintained by antimicrobial peptides (AMPs) expressed in the epithelial and immune cells. AMPs are also identified as immune-regulators in various diseases. Previous studies demonstrated that deficiency of AMPs REG3 lectins exacerbated alcoholic steatohepatitis. LL-37 is the sole member of human cathelicidin AMP family, named CRAMP in mouse. Despite of the extensive studies in infectious diseases and in gut-microbiota-related inflammatory bowel disease, the role of LL-37/CRAMP in ALD is yet unknown. Our previous studies showed a decreased intestinal CRAMP in a mouse model …
Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller
Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller
Electronic Theses and Dissertations
The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …
A Model To Study The Effects Of Whole Life Chronic Exposure To Arsenic Or Cadmium On The Development Of Adult Metabolic Syndrome : Initial Characterization Of Hepatic Changes., Jamie L. Young
Electronic Theses and Dissertations
Metabolic syndrome (MetS) is a group of diseases affecting < 30% of adults. Although obesity is a major risk for the development of MetS, it does not account for all cases, suggesting contribution of other risk factors. We hypothesized that early life exposure to arsenic (As) or cadmium (Cd) may represent such a risk. The purpose of this study was to characterize a model to discern the effects of early life exposures to Cd and As on high fat diet (HFD)-induced MetS. Adult C57BL/6J mice were exposed to control or metals containing drinking water. Pregnant dams and offspring were continuously exposed to the same toxicants as their parents. At weaning, offspring were fed LFD or HFD and sacrificed 10 or 24 weeks later. Metal exposure caused time- and sex-dependent alterations in HFD-induced variables of liver damage. The initial results suggest that these toxicants enhanced obesity-induced liver injury.
The Effects Of Polychlorinated Biphenyls Exposure On Non-Alcoholic Fatty Liver Disease : Role Of Aryl Hydrocarbon Receptor., Hongxue Shi
Electronic Theses and Dissertations
Polychlorinated biphenyls (PCBs) are detectable in serum of 100% of adults in US, and has been associated with fatty liver disease in epidemiological studies. PCBs are classified as either dioxin-like (DL) or non-dioxin-like (NDL) PCB based on their ability to activate the aryl hydrocarbon receptor (AhR). We used exposures that reflect human bioaccumulation patterns, which resembles Aroclor 1260 with a low level of the DL-PCB, PCB 126. Our aim was to determine if this exposure will activate the human and mouse AhR and examine if receptor activation influences these steatotic responses due to PCB exposures. DL-PCBs exposure-induced AhR activation in …
Vinyl Chloride Enhances Diet-Induced Liver Injury Via Metabolic Dyshomeostasis : Critical Role Of Mitochondria., Anna L. Lang
Vinyl Chloride Enhances Diet-Induced Liver Injury Via Metabolic Dyshomeostasis : Critical Role Of Mitochondria., Anna L. Lang
Electronic Theses and Dissertations
Background. Vinyl chloride (VC) is an environmental toxicant and has been shown to be directly hepatotoxic at high exposures. However, recent studies suggest low-level toxicant exposure can cause subtle changes to the liver. Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the United States, it is important to determine the impact of low-level toxicant exposure on the progression of underlying liver injury when combined with other factors. Therefore, the overarching goal of this dissertation was to develop a model of VC co-exposure with high-fat diet (HFD) and to determine the mechanisms by which VC contributes to the …