Toxicology Commons^™

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 …

The Combined Neuropharmacology And Toxicology Of Major 'Bath Salts' Constituents Mdpv, Mephedrone, And Methylone, Serena Allen

Electronic Theses and Dissertations

The synthetic cathinones, 3,4- methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4- methylenedioxymethcathinone (methylone), gained worldwide notoriety as the psychoactive components of ‘bath salts;’ a marketing term used to circumvent federal drug laws and permit their legal sale. Previous studies have shown that these drugs share pharmacological characteristics with cocaine and the amphetamines, however, descriptions of their neurotoxic properties are limited. Moreover, while forensic analysis has revealed that the most frequently abused bath salts ‘brands’ contain binary and ternary mixtures of MDPV, mephedrone, and methylone, the majority of preclinical research has focused on explicating the individual effects of these drugs. Therefore, the …

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.

Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI), an abrupt loss of kidney function which carries a high mortality and confers an increased risk of chronic kidney disease, develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent [1], [2], [3]. The sodium hydrogen exchange regulatory factor isoform 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins, in renal proximal tubules [4]. NHERF-1 deficient mice have aberrant localization of BBM proteins in intracellular compartments [5]. The investigators have recently demonstrated NHERF1 deficient proximal tubule cells have an underlying …

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 …

Lead, Copper, And Iron In University Tap Water, Alison Mclendon

Honors Theses

This study observed concentrations of lead, copper, and iron in university tap water over an eight-week span during and between the summer and fall semesters. First draw and 30s flush samples were taken after overnight stagnation from the Honor House, College Hall, J. B. George Building, and International Center bathrooms and analyzed with an inductively-coupled plasma mass spectrometer (ICPMS). There was no obvious correlation between time in the semester and metal concentrations. Relative iron levels rose and fell at the same time in all buildings, but there was little correlation between buildings for lead and copper concentrations. The Honor House …

The Combined Effects Of Atrazine And Tetracycline On Primary Producers And Zooplankton In Freshwater Microcosms, Madison R. Kelly

Honors College Theses

Widespread use of agrochemicals such as herbicides and antibiotics increases their likelihood of entering aquatic systems in mixture. Despite different modes of action, atrazine (herbicide) and tetracycline (antibiotic) adversely affect non-target photosynthetic organisms, such algae and macrophytes, with the potential to reduce food availability to higher trophic levels. However, the effects of simultaneous exposure to both contaminants have yet to be determined. I hypothesized that a mixture of atrazine and tetracycline affects freshwater communities differently than each compound alone. A microcosm experiment was conducted to test effects of environmentally relevant concentrations of atrazine (1 μg L^-1) and tetracycline …

Evaluating The Aryl Hydrocarbon Receptor As A Target For Pharmacologic Activity Of Repurposed Drugs, Teofilo Borunda Duque

Pharmaceutical Sciences ETDs

The discovery of new pharmacologic targets is important for the advancement of pharmacotherapy and identification of new indications for current drugs. The aryl hydrocarbon receptor (AHR) is a physiologic sensor of both chemical environmental pollutants and ligands of natural origin. Given the broad spectrum of ligands that activate the AHR and its relationship with toxicology, the AHR is not thought to be a traditional target for pharmacotherapy. However, multiple studies have shown potential for the AHR as a novel pharmacologic target Therefore, identifying less toxic agents that modulate the AHR may elucidate mechanisms for pharmacological targeting of the AHR. The …

Effects Of Radiation On Neurite Morphology And Cytoskeleton Structure, Melissa Sassman

Student Scholarship

Long-term manned space exploration to the moon, Mars, and other areas beyond Earth's protective magnetic field poses possible acute and late central nervous systems (CNS) risks. Of particular concern for astronauts is exposure to high atomic number, high energy particles known as HZE particles, a component of galactic cosmic radiation (GCR). Although NASA has radiation safety requirements, the possible effects of GCR and HZE particles on the central nervous systems of astronauts remains unknown. Understanding the risks and effects of galactic cosmic radiation and HZE particles on the central nervous system will allow for safer space exploration.

Additionally, and perhaps …

Contractile Response Of Bovine Lateral Saphenous Vein To Ergotamine Tartrate Exposed To Different Concentrations Of Molecularly Imprinted Polymer, Manoj B. Kudupoje, James L. Klotz, Alexandros Yiannikouris, Karl A. Dawson, Kyle R. Mcleod, Eric S. Vanzant

Animal and Food Sciences Faculty Publications

Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response …

Determination Of Selected Aromas In Marquette And Frontenac Wine Using Headspace-Spme Coupled With Gc-Ms And Simultaneous Olfactometry, Somchai Rice, Nanticha Lutt, Jacek A. Koziel, Murlidhar Dharmadhikari, Anne Fennell Dr

Agronomy, Horticulture and Plant Science Faculty Publications

Understanding the aroma profile of wines made from cold climate grapes is needed to help winemakers produce quality aromatic wines. The current study aimed to add to the very limited knowledge of aroma-imparting compounds in wines made from the lesser-known Frontenac and Marquette cultivars. Headspace solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) with simultaneous olfactometry was used to identify and quantify selected, aroma-imparting volatile organic compounds (VOC) in wines made from grapes harvested at two sugar levels (22° Brix and 24° Brix). Aroma-imparting compounds were determined by aroma dilution analysis (ADA). Odor activity values (OAV) were also used to …

Regulation Of Radioactive Fracking Waste, Elizabeth Ann Glass Geltman, Nichole Leclair

Publications and Research

Natural gas extracted form shale reached record production totals in 2015 in the United States and the US Energy Information Administration (EIA) forecasts natural gas production will continue to increase. Wastes from shale gas extraction can contain the radioactive isotopes radium-226 (Ra-226) and radium-228 (Ra-228), which decay further into radon (Rn). Exposure to radon, a form of naturally occurring radioactive materials (NORM), is the leading cause of lung cancer in the United States, after smoking. This article explores how states handle the disposal of technologically enhanced naturally occurring radioactive materials (TENORM) and/or NORM waste from oil and gas operations to …

An Optimized Solid-Phase Reduction And Capture Strategy For The Study Of Reversibly-Oxidized Cysteines And Its Application To Metal Toxicity, John Andrew Hitron

Theses and Dissertations--Toxicology and Cancer Biology

The reversible oxidation of cysteine by reactive oxygen species (ROS) is both a mechanism for cellular protein signaling as well as a cause of cellular injury and death through the generation of oxidative stress. The study of cysteine oxidation is complicated by the methodology currently available to isolate and enrich oxidized-cysteine containing proteins. We sought to simplify this process by reducing the time needed to process samples and reducing sample loss and contamination risk.

We accomplished this by eliminating precipitation steps needed for the protocol by (a) introducing an in-solution NEM-quenching step prior to reduction and (b) replacing soluble dithiothreitol …

The Influence Of Physiological And Abiotic Factors On The Sensitivity Of The Sea Lamprey (Petromyzon Marinus) To The Lampricide 3-Trifluoromethyl-4-Nitrophenol (Tfm), Alexandra Muhametsafina

Theses and Dissertations (Comprehensive)

Invasive sea lamprey (Petromyzon marinus) in the Great Lakes are controlled using the pesticide (lampricide) 3-trifluoromethyl-4-nitrophenol (TFM), which is applied to nursery streams containing larval lamprey. The toxicity of TFM to lamprey is affected by various environmental and physiological factors, which can lead to residual lamprey that survive TFM treatment. The goal of this study was to investigate how abiotic (season and temperature) factors interacted with physiological parameters (whole body and tissue energy reserves) to influence TFM sensitivity in sea lamprey. Toxicity tests were conducted at different times of the year (spring, early and late summer, fall) and …

Impact Of Physico-Chemical Properties Of Manufactured Nanomaterials On Plant Uptake And Trophic Transfer, Jieran Li

Theses and Dissertations--Toxicology and Cancer Biology

Large quantities of manufactured nanomaterials (MNM) are released into the environment by human activity each year. The entry of MNM into the terrestrial food webs, which has the potential for far-reaching impacts, begins with the uptake by plant species from the soil. These processes can be affected by MNM physico-chemical properties such as size, chemical composition, surface charge, etc., of which our knowledge is still incomplete. To bridge some of the gaps in our understanding of these processes and, specifically, to determine whether the physico-chemical properties of the MNM are predictive of their behavior in terrestrial food chains, we conducted …

Pcb Disruption Of Gut And Host Health: Implications Of Prebiotic Nutritional Intervention, Jessie Baldwin Hoffman

Theses and Dissertations--Pharmacology and Nutritional Sciences

Exposure to environmental pollutants poses numerous risk factors for human health, including increasing incidence of cardiovascular disease and diabetes. Persistent organic pollutants, such as polychlorinated biphenyls (PCBs) have been strongly linked to the development of these chronic inflammatory diseases and the primary route of exposure is through consumption of contaminated food products. Thus, the gastrointestinal tract is susceptible to the greatest levels of these pollutants and is an important facet to study.

The first two hypotheses of this dissertation tested that exposure to PCBs disrupts gut microbiota directly (in vitro) and within a whole body system. PCB exposure …

Test Of Bpa's Estrogenic Effects On Brain Aromatase Expression, Neural Activity, And Locomotive Behavior In Zebrafish Larvae, Ryan J. Mcauley

Cal Poly Humboldt theses and projects

Bisphenol A (BPA) is a well-known endocrine disrupting chemical that mimics the effects of estrogens. Aromatase B (Cyp19a1b) is a brain-specific enzyme that converts testosterone to estrogen and is highly upregulated in response to estrogen receptor activation localized to radial glial cells. During embryonic zebrafish development, there is a small window of time denoted by an increase in neurogenesis and estrogen receptor activity. Previous studies have demonstrated that a low dose BPA exposure (0.1µM) during this window causes hyperlocomotion in larval zebrafish, yet no further explanation for this behavior change has been described. The purpose of this study was to …

Sensitivity Of Quagga Mussels (Dreissena Rostriformis Bugensis) To Cyanobacteria At Multiple Life History Stages, Anna Boegehold

Wayne State University Dissertations

Quagga mussels (Dreissena rostriformis bugensis) originate from brackish waters of the Ponto-Caspian area and are nuisance invasive species in North American and European freshwaters. Their invasion has caused major economic and ecological damages in the Laurentian Great Lakes. Through selective filter feeding, quagga mussels have promoted the growth of cyanobacteria. Harmful cyanobacteria blooms have the potential to produce toxins, which can be toxic to humans and wildlife. Although quagga mussels can increase the prevalence of cyanobacteria blooms, it is unknown how they are physiologically affected by cyanobacteria and understanding these dynamics can be useful in the management of this invasive …

Design, Synthesis And Biological Evaluation Of Inhibitors Against Both Human And Mouse Microsomal Prostaglandin E2 Synthase-1 Enzymes, Kai Ding

Theses and Dissertations--Chemistry

As the principal pro-inflammatory prostanoid, prostaglandin E₂ (PGE₂) serves as mediator of pain and fever in inflammatory reactions. The biosynthesis of PGE₂ starts from arachidonic acid (AA). Cyclooxygenase (COX)-1 and/or COX-2 converts AA to prostaglandin H₂ (PGH₂), and PGE₂ synthases transform PGH₂ to PGE₂. Current mainstream approach for treating inflammation-related symptoms remains the application of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective COX-2 inhibitors (coxibs). As both categories shut down the biosynthesis of all downstream prostanoids, their application renders several deleterious effects including gastrointestinalulceration and cardiovascular risk. Microsomal prostaglandin …

The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, Julia Grzymkowski, Christopher J. Ehrhardt, Justin L. Poklis, Michelle R. Peace

UROP Posters

There has been an increase in use of Traditional Chinese Medicine (TCM) in the United States because they are less expensive and believed to be more effective with less adverse effects in comparison to traditional pharmaceutics. Therefore, sales have increased in the US, despite articles and case studies demonstrating the dangers, such as injury and death, related to TCM, stemming from improper labelling, toxic contaminants, and, in some cases, the presence of pathogenic bacteria. The aim of this study was to perform a survival experiment to demonstrate the importance of proper herbal brewing technique and to conduct a molecular and …

Forensic Markers Of Lampricide Toxicity In Oncorhynchsus Mykiss, Chris White

Theses and Dissertations (Comprehensive)

The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) has been used for decades to control invasive sea lamprey (Petromyzon marinus) populations in the Great Lakes, normally with little harm to other fish populations. However, due to the nature of lampricide treatments and the chemical properties of TFM, adverse effects to non-target fishes and non-target mortality occasionally occur. However, investigations of non-target mortality can be complex, particularly if fish deaths are not noticed immediately, due to decomposition of the carcasses. The objectives of this thesis were to expose rainbow trout (Oncorhynchsus mykiss) to TFM in order to: (i) identify forensic markers …

Fate Of Methoprene In Temperate Salt Marsh Ditches Following Aerial Applications, David J. Tonjes, Anne E. Mcelroy, Robin K. Barnes, Dominick V. Ninivaggi, Walter Dawydiak, Gregory T. Greene, Bruce J. Brownawell

Technology & Society Faculty Publications

Aerial applications of liquid methoprene are used in salt marshes to control mosquitoes by preventing adult emergence. Despite concern about toxicity to non-target organisms, little is known about environmental concentrations after applications, nor methoprene's persistence in salt marsh environments. Aqueous and sediment samples were collected from two marshes receiving weekly applications. Aqueous samples were collected as early as 30 minutes after applications and as long as nine days afterwards; sediment samples were taken within hours of application and as long as 19 days post-application. Use of time-of-flight liquid chromatography – mass spectral analysis allowed for ultra low detection limits (0.5 …

Remobilization Of Heavy Metals By Mangrove Leaves, Hanan Almahasheer, Oscar Serrano, Carlos M. Duarte, Xabier Irigoien

Research outputs 2014 to 2021

Several studies have been carried out on heavy metal pollution in mangrove ecosystems. However, the role of mangroves in heavy metal remobilization is still relatively unknown. On one side, mangrove woody organs and soils sequester heavy metals for long time periods, but on the other hand, senescence of mangrove leaves may return these metals collected by roots to the upper layers of the soil. Here, we analyzed the concentration of chemical elements (Al, As, Cd, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sr, V, and Zn) as a function of age in mangrove leaves to understand heavy metals retention by …

The Effects Of The Red Tide Producing Dinoflagellate, Karenia Brevis, And Associated Brevetoxins On Viability And Sublethal Stress Responses In Scleractinian Coral: A Potential Regional Stressor To Coral Reefs, David A. Reynolds

UNF Graduate Theses and Dissertations

Coral cover is in decline on a global scale, with increased mortality events being attributed to a number of global and regional stressors. While the impacts of global stressors (e.g. sea surface temperature rise, ocean acidification) are well documented, there is growing interest in identifying and understanding the impacts of regional stressors. The reason for this change in focus is that regional stressors can often work in combination, sometimes synergistically, with global stressors and that stressors on a regional scale tend to be more easily mitigated by management practices. One regional stressor that impacts a myriad of marine organisms in …

Effects Of Unweathered Or Soil Weathered Copper-Based Nanoparticles And Compounds On Soil Grown Bell Pepper (Capsicum Annuum) And Spinach (Spinacia Oleracea) Plants, Swati Rawat

Open Access Theses & Dissertations

Engineered nanoparticles (ENPs) find large scale industrial application because of their promising chemical, physical, electrical, magnetic, optical, and electronic properties. Copper-based ENP are used as gas sensors, in catalysts, electronics, semi-conductors, and in agriculture. They have been useful as agricultural amendments in the form of pesticides, herbicides, and fertilizers because of their antifungal and antibacterial properties. They also find application in electronics and sensors used in precision agriculture. Due to their massive production and use, ENPs are likely to be ubiquitous in the environment around us in the near future. Application of biosolids for fertilization and water from wastewater treatment …

Testing The Underlying Chemical Principles Of The Biotic Ligand Model (Blm) To Marine Copper Systems: Measuring Copper Speciation Using Fluorescence Quenching, Tara N. Tait, James C. Mcgeer, Scott Smith

Chemistry Faculty Publications

Speciation of copper in marine systems strongly influences the ability of copper to cause toxicity. Natural organic matter (NOM) contains many binding sites which provides a protective effect on copper toxicity. The purpose of this study was to characterize copper binding with NOM using fluorescence quenching techniques. Fluorescence quenching of NOM with copper was performed on nine sea water samples. The resulting stability con- stants and binding capacities were consistent with literature values of marine NOM, show- ing strong binding with log K values from 7.64 to 10.2 and binding capacities ranging from 15 to 3110 nmole mg C ^{−1 …}

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.

Effects Of Crude Oil On Tumor Suppressor P53 Polymorphisms In Laboratory-Exposed Atlantic Killifish, Fundulus Heteroclitus, Allison Margaret Nadler

Seton Hall University Dissertations and Theses (ETDs)

Polycyclic aromatic hydrocarbons (PAHs), constituents of crude oil, are implicated as a potent source of adverse toxicological effects on living organisms. To model the effects of PAHs in response to environmental oil spill disasters a species of killifish (Fundulus heteroclitus) was captured and exposed to crude oil in a laboratory-controlled setting. Over a period of 7 days, fish were dosed with crude oil by gavage, culled, and organs were harvested for analysis. Excitation-emission matrix spectroscopy (EEMS) of gall bladder tissue homogenates was used to verify exposure. Effects of PAHs on the p53 gene were evaluated as an indicator …

Organizational Effects Of Defeminizing Toxicants: Lessons Learned From An Environmental Sentinel Organism, The Fathead Minnow., Jonathan Ali

Theses & Dissertations

Endocrine disrupting compounds (EDCs) are chemicals that interfere with hormone function and are increasingly detected in aquatic environments, where they elicit adverse effects from exposed organisms. The toxicological effects of EDCs can be described as either activational (reversible) or organizational (irreversible), where the latter are associated with adverse outcomes in reproductive performance of adult fish. However, few studies have investigated the organizational impacts of anti-estrogenic or “defeminizing” EDCs, e.g. agrichemicals or pharmacological agents, in an environmentally-relevant or “sentinel” species. The objective of this study was to investigate the impacts of early-life EDC-initiated changes in estrogenic gene expression on organizational effects …

Identification And Quantification Of Cyanide And Its Metabolites In Lemur Urine, Jeremy Peralta

Student Theses

Cyanide is a chemical compound that contains the monovalent groups of carbon and nitrogen. This substance is considered a rapidly acting deadly chemical. However, some animals such as lemurs consume food products that are known to contain elevated levels of cyanide without major consequences. The mechanism by which the lemur can handle this high exposure to cyanide is unknown. In this study, we developed and validated two analytical methods for the determination of cyanide and two metabolites, thiocyanate and 2-aminothiazoline-4-carboxylic acid (ATCA) in lemur urine. The method was applied to 47 authentic lemur urine samples collected from 4 different species …