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Articles 1 - 30 of 69
Full-Text Articles in Toxicology
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 …
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 …
Wastewater-Informed Public Health Intervention Playbook
Wastewater-Informed Public Health Intervention Playbook
Sustain Magazine
As the SARS-CoV-2 pandemic quickly spread from country to country and continent to continent in 2020, governments and scientists needed a way to track COVID-19 through populations in order to position public health interventions in the most impactful locations. Having a decision-based risk framework may help to guide policy creation that could minimize or prevent possible outbreaks and surges of infection within communities. The University of Louisville in partnership with Louisville’s Department of Public Health and Wellness tested this strategy in 2021 and 2022. This Wastewater-Informed Public Health Intervention Playbook describes the decisions and actions of that academic and public …
The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.
The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.
Faculty Scholarship
We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one’s 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of …
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 …
How A Low-Cost Method For Cumulative Water-Sampling Shows Need For Improvement Of Legal Public-Contact Standards In The United States, Samuel C. Kessler
How A Low-Cost Method For Cumulative Water-Sampling Shows Need For Improvement Of Legal Public-Contact Standards In The United States, Samuel C. Kessler
Grawemeyer Colloquium Papers
Across the world, it is estimated that 4.5 billion people live near water sources “impaired” for use or contact. Standards for human-interaction are established by international organizations such as the WHO, and legislative bodies from national to local levels with jurisdiction over the quality of our waterways to ensure public & environmental health. Standards are often assessed from “grab-samples” taken from a waterbody at a certain time, with a minimum number analyzed. Water-quality standards in the United States are enforced under the Clean Water Act (CWA) via the Environmental Protection Agency (EPA), applying to “waters of the United States” (WOTUS). …
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 …
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-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 …
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 …
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. …
Sustainable Solutions, Fall/Winter 2020, Issue 41
Sustainable Solutions, Fall/Winter 2020, Issue 41
Sustain Magazine
No abstract provided.
Environmentally Responsible Land Use, Spring/Summer 2010, Issue 22
Environmentally Responsible Land Use, Spring/Summer 2010, Issue 22
Sustain Magazine
No abstract provided.
Sustainable Communities, Fall/Winter 2010, Issue 21
Sustainable Communities, Fall/Winter 2010, Issue 21
Sustain Magazine
No abstract provided.
Sustainable Building, Spring/Summer 2009, Issue 20
Sustainable Building, Spring/Summer 2009, Issue 20
Sustain Magazine
No abstract provided.
Environmental History, Fall/Winter 2009, Issue 19
Environmental History, Fall/Winter 2009, Issue 19
Sustain Magazine
No abstract provided.
Student Research, Spring/Summer 2008, Issue 18
Evolving Pollution Prevention, Fall/Winter 2008, Issue 17
Evolving Pollution Prevention, Fall/Winter 2008, Issue 17
Sustain Magazine
No abstract provided.
Climate Change, Spring/Summer 2007, Issue 16
Our Energy Future, Fall/Winter 2007, Issue 15
Land Conservation, Spring/Summer 2006, Issue 14
Land Conservation, Spring/Summer 2006, Issue 14
Sustain Magazine
No abstract provided.
Pollution And Heart Disease, Fall/Winter 2006, Issue 13
Pollution And Heart Disease, Fall/Winter 2006, Issue 13
Sustain Magazine
No abstract provided.