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 Department: Department of Biological Sciences
 Collection: UNT Theses and Dissertations
The Effect of Menthol on Nicotine Metabolism:  a Cross Species Evaluation

The Effect of Menthol on Nicotine Metabolism: a Cross Species Evaluation

Date: December 2013
Creator: Pace, Wendy Lee
Description: The effect of menthol on nicotine metabolism was examined in liver S9 fractions of four different species and in the in vivo mouse model. The purpose of this study was to investigate three parameters: (1) biotransformation of nicotine to cotinine in various species (human, mouse, rat and trout) using in vitro methods; (2) to determine if the addition of menthol with nicotine altered biotransformation of nicotine to cotinine; (3) and to assess similar parameters in an in vivo mouse model. The major findings of this study include: (1) mice appear to metabolize nicotine, over time, in a manner similar to humans; (2) menthol decreased cotinine production, over time, after a single dose in mice; and (3) menthol increased cotinine production, over time, after repeated doses, in mice.
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Effects of Airway Pressure, Hypercapnia, and Hypoxia on Pulmonary Vagal Afferents in the Alligator (Alligator Misssissippiensis)

Effects of Airway Pressure, Hypercapnia, and Hypoxia on Pulmonary Vagal Afferents in the Alligator (Alligator Misssissippiensis)

Date: December 2013
Creator: Marschand, Rachel E.
Description: The American alligator (Alligator mississippiensis) is an aquatic diving reptile with a periodic breathing pattern. Previous work has identified pulmonary stretch receptors (PSR), both rapidly- and slowly-adapting, and intrapulmonary chemoreceptors (IPCs) that modulate breathing patterns in alligators. The purpose of the present study was to identify the effects of prolonged lung inflation and deflation (simulated dives) on PSR and/or IPC firing characteristics in the alligator. The effects of airway pressure, hypercapnia, and hypoxia on dynamic and static responses of pulmonary stretch receptors (PSR) were studied in juvenile alligators (mean mass = 246 g) at 24°C. Receptor activity appeared to be a mixture of slowly-adapting PSRs (SARs) and rapidly-adapting PSRs (RARs) with varying thresholds and degrees of adaptation, but no CO2 sensitivity. Dives were simulated in order to character receptor activity before, during, and after prolonged periods of lung inflation and deflation. Some stretch receptors showed a change in dynamic response, exhibiting inhibition for several breaths after 1 min of lung inflation, but were unaffected by prolonged deflation. For SAR, the post-dive inhibition was inhibited by CO2 and hypoxia alone. These airway stretch receptors may be involved in recovery of breathing patterns and lung volume during pre- and post-diving behavior and ...
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Field and Laboratory Fish Tissue Accumulation of Carbamazepine and Amiodarone

Field and Laboratory Fish Tissue Accumulation of Carbamazepine and Amiodarone

Date: December 2013
Creator: García Martínez, Santos Noé
Description: The goals of this dissertation work were to assess the bioaccumulation potential of carbamazepine and amiodarone, two widely used ionizable pharmaceutical compounds that possess mid-range and high LogD values, respectively, and to evaluate alternative methods to assess chemical accumulation in bluntnose minnows, catfish, and tilapia. Results indicated that carbamazepine does not appreciably bioaccumulate in fish tissue with BCFk and BAF carbamazepine values < 10. Amiodarone, however, with a log D of 5.87 at pH 7.4, accumulated in fish tissues with kinetic BCF values <2,400. Collectively, the data suggest that full and abbreviated laboratory-derived BCFs, BCFMs derived from S9 loss-of-parent assays, as well as field BAF values are similar for each of the two drugs. In summary, the results from this dissertation indicated: 1) The reduced design BCF test is a good estimate for the traditional OECD 305 test. 2) In vitro S9 metabolism assays provide comparable BCF estimates to the OECD 305 test. 3) Metabolism may play a large role in the accumulation of drugs in fish. 4) Reduced BCF tests and in vitro assays are cost effective and can reduce vertebrate testing.
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Investigation of the Pharmacokinetics of Diazepam in Juvenile Channel Catfish (Ictalurus Punctatus)

Investigation of the Pharmacokinetics of Diazepam in Juvenile Channel Catfish (Ictalurus Punctatus)

Date: December 2013
Creator: Overturf, Carmen L.
Description: The presence of pharmaceuticals in the environment is becoming an increasing regulatory and scientific concern. Thus, the metabolic profile and bioconcentration potential of diazepam, a model benzodiazepine, were examined, as well as effects on the endocrine system in channel catfish. Through the use of specific and non-specific cytochrome P450 (CYP450) inhibitors, it was determined that CYP3A-like enzymes may play a role in the biotransformation of diazepam into temazepam; however, the isoform(s) required for the formation of other metabolites is still unknown. Overall, only around 7-8% of diazepam is biotransformed into two known metabolites. Due to the lack of inherent metabolism of diazepam in channel catfish, further analysis was conducted to determine the tissue-specific bioconcentration potential of diazepam in catfish. Various tissues were analyzed for the presence of diazepam as well as metabolites and bioconcentration factors (BCF) were calculated, which were all well below regulatory threshold values (> 2000). Additionally, modulation of the endocrine system by diazepam was examined by measuring steroid hormone concentrations and analyzing mRNA expression of selected steroidogenic enzymes and receptors. Two steroidogenic enzymes were modulated following diazepam exposure, indicating potential endocrine disrupting properties of diazepam. Together, these data suggest that diazepam exhibits low metabolic transformation rates in ...
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Modeling the Effects of Chronic Toxicity of Pharmaceutical Chemicals on the Life History Strategies of Ceriodaphnia Dubia:  a Multigenerational Study

Modeling the Effects of Chronic Toxicity of Pharmaceutical Chemicals on the Life History Strategies of Ceriodaphnia Dubia: a Multigenerational Study

Date: December 2013
Creator: Lamichhane, Kiran
Description: Trace quantities of pharmaceuticals (including carbamazepine and sertraline) are continuously discharged into the environment, which causes concern among scientists and regulators regarding their potential long-term impacts on aquatic ecosystems. These compounds and their metabolites are continuously interacting with the orgranisms in various life stages, and may differentially influence development of embryo, larvae, juvenile, and adult stages. To fully understand the potential ecological risks of two candidate pharmaceutical chemicals (carbamazepine (CBZ) and sertraline (SERT)) exposure on survival, growth and reproduction of Ceriodaphnia dubia in three sucessive generations under static renewal toxicity test, a multigenerational approach was taken. Results indicate that SERT exposure showed higher sensitivity to chronic exposure to C. dubia growth and reproduction than CBZ exposure. The lowest concentration to affect fecundity and growth was at 50 µg L-1 SERT in the first two generations. These parameters become more sensitive during the third generation where the LOEC was 4.8 µg L-1. The effective concentrations (EC50) for the number of offspring per female, offspring body size, and dry weight were 17.2, 21.2, and 26.2 µg SERT L-1, respectively. Endpoints measured in this study demonstrate that chronic exposure of C. dubia to SERT leads to effects that occur at concentrations an order ...
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Population Dynamics of Zebra Mussels (Dreissena Polymorpha) in a North Texas Reservoir: Implications for Invasions in the Southern United States

Population Dynamics of Zebra Mussels (Dreissena Polymorpha) in a North Texas Reservoir: Implications for Invasions in the Southern United States

Date: December 2013
Creator: Churchill, Christopher J.
Description: This dissertation has two main objectives: first, quantify the effects of environmental conditions on spatio-temporal spawning and larval dynamics of zebra mussels (Dreissena polymorpha [Pallas 1771]) in Lake Texoma, and second, quantify the effects of environmental conditions on survival, growth, and reproduction of young of the year (YOY) juvenile zebra mussels. These biological responses directly influence population establishment success and invasive spread dynamics. Reproductive output of the zebra mussel population in Lake Texoma was significantly related to water temperature and lake elevation. Annual maximum larval (veliger) density decreased significantly indicating a population crash, which was likely caused by thermal stress and variability of lake elevation. In 2011, temperatures peaked at 34.3°C and lake elevation decreased to the lowest level recorded during the previous 18 years, which desiccated a substantial number of settled mussels in littoral zones. Estimated mean date of first spawn in Lake Texoma was observed approximately 1.5 months earlier than in Lake Erie, and peak veliger densities were observed two months earlier. Veligers were observed in the deepest oxygenated water after lake stratification. During a 69-day in situ experiment during summer in Lake Texoma, age-specific mortality of zebra mussels was generally high until temperatures decreased to approximately 28°C, ...
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Relationships of Benthic Macroinvertebrate Community Structure with Land-use, Habitat, In-stream Water Chemistry, Depositional Sediment Biofilm Fatty Acids, and Surfactants in the Effluent Dominated Texas Trinity River

Relationships of Benthic Macroinvertebrate Community Structure with Land-use, Habitat, In-stream Water Chemistry, Depositional Sediment Biofilm Fatty Acids, and Surfactants in the Effluent Dominated Texas Trinity River

Date: December 2013
Creator: Slye, Jaime L.
Description: The Trinity River is an urbanized, effluent-dominated river, and is heavily relied upon for drinking water. The benthic macroinvertebrate community has been monitored for over 20 years, with the focus of this dissertation on three studies (1987-88, 2005, and 2011). Water quality improvement following dechlorination resulted in increased benthic metrics. Overall habitat quality, in-stream cover, surface water total organic carbon, sediment total organic carbon, near-field urban land-use, near-field forested land-use, surface water surfactant toxic units, and depositional sediment biofilm fatty acids all have statistically significant relationships with benthic macroinvertebrate metrics. These relationships are better defined with increased taxonomic resolution at the genus/species level for all benthic taxa, including Chironomidae and Oligochaeta. It is recommend that benthic identifications for state and city water quality assessments be done at the genus/species level. A novel method for quantifying depositional sediment biofilm fatty acids has been produced and tested in this dissertation. Benthic metrics are directly related to fatty acid profiles, with several essential fatty acids found only at upstream sites.
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Shortened in Vivo Bioconcentration Factor Testing in Cyprinus Carpio

Shortened in Vivo Bioconcentration Factor Testing in Cyprinus Carpio

Date: December 2013
Creator: Cantu, Mark
Description: Bioconcentration factor testing serves as the most valuable surrogate for the assessment of bioaccumulation. The assessment of potentially harmful chemicals is crucial to not only the health of aquatic environments, but to humans as well. Chemicals that possess the ability to persist in the environment or that have the potential to bioaccumulate, pose a greater risk to organisms that are exposed to these chemicals. The Organization for Economic Cooperation and Development Guideline 305 outlines specific protocols to run an accurate and reliable aquatic flow-through test. However, since its adoption in 1996, very few changes have been made to accommodate the endeavor to lowering the amount of test species to run one of these said tests. Running an aquatic flow-through test, according to 305, takes much time and money as well as numerous amounts of fish. Such burdens can be eliminated through simple modifications to the standard protocols. In this study, we propose an abbreviated study design for aquatic bioconcentration testing which effectively alleviates the burdens of running a flow-through test. Four chemicals were used individually to evaluate the usefulness of the proposed shortened design; 4-Nonyphenol, Chlorpyrifos, Musk Xylene, and DDT. The study consisted of exposing Cyprinus carpio for 7 days ...
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Comparative Phyto-uptake Across Distribution Coefficients of Pharmaceutical Compounds and Aquatic Macrophytes: Carbamazepine and Amiodarone Uptake in Lemna Spp

Comparative Phyto-uptake Across Distribution Coefficients of Pharmaceutical Compounds and Aquatic Macrophytes: Carbamazepine and Amiodarone Uptake in Lemna Spp

Date: August 2013
Creator: Woodard, Jennifer Kristin
Description: Few studies have been conducted on the effectiveness of phytoremediation of pharmaceutical compounds, although the persistent and non-acutely toxic nature of many of these compounds in today's water bodies may yield an ideal application for this practice. To quantify the potential effectiveness of plant uptake, kinetic and proportional bioconcentration factors (BCFk, and BCFp, respectively) in nanograms (ng) carbamazepine and amiodarone per gram (g) wet weight plant tissue for Lemna spp. were determined utilizing a 14-day continuous flow-through study. Samples were analyzed using isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) running in positive ion mode. Kinetic BCF was estimated at 0.538, while proportional BCF was estimated at 0.485. Kinetic BCF for the amiodarone study was estimated at 23.033, whereas proportional BCF was estimated at 41.340. Possible contamination of the C18 column and peristaltic pump failure may have impacted uptake results. In light of variability and current lack of research in the field, this work should be considered exploratory rather than conclusive.
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Endocrine Disruption of Levonorgestrel in Early-life Stages of Fathead Minnows, Pimephales Promelas

Endocrine Disruption of Levonorgestrel in Early-life Stages of Fathead Minnows, Pimephales Promelas

Date: August 2013
Creator: Overturf, Matthew D.
Description: Pharmaceuticals have routinely been detected in the environment resulting in a growing concern about whether these drugs could elicit effects on aquatic organisms. The concerns are centered on the highly conserved nature of mammalian therapeutic targets in fish. These pharmaceuticals are found at very low levels in the environment, which can result in sub-lethal effects in aquatic organisms. Therefore, 28 d early-life stage studies were conducted on six pharmaceuticals to assess their impacts on survival and growth fathead minnow larvae. Two pharmaceuticals tested, carbamazepine and fenofibrate, resulted in no alterations to survival and growth. However, amiodarone, clozapine, dexamethasone, and levonorgestrel (LNG) reduced survival at concentrations tested with LNG being the most potent at 462 ng/L. Survival was increased with amiodarone and clozapine; however LNG significantly decreased growth at 86 ng/L. Therefore, the most potent pharmaceutical tested was the synthetic progestin LNG with survival and growth impacts at concentrations less than 1 μg/L. Further analysis was conducted by measuring specific endocrine related mRNA transcript profiles in FHM larvae following the 28 d ELS exposure to LNG. Transcripts of 3β-HSD, 20β-HSD, and FSH were significantly down-regulated following 28 d exposure to both 16.3 and 86.9 ng/L LNG. Also, CYP19a expression was significantly ...
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