University of Mississippi
School of Pharmacy Environmental Toxicology Research Program

Environmental Toxicology Research Program

Research in Progress

Environmental

The primary research interest of ETRP scientists is related to environmental health in aquatic and marine ecosystems. This research spans the spectrum from molecular/cellular biomarkers of stress to population- and community-level responses, as well as adaptations to stressors.

  • Seagrass Community Resilience to Natural and Anthropogenic Stressors.
The Gulf of Mexico coastline has seen increased stress in recent years from extreme storm events (i.e., Hurricanes Katrina and Rita; 2005). Seagrass communities are incredibly important ecosystems that act as a nursery ground for commercial species, a buffer for coastal communities, and habitat for rare/endangered species. ETRP scientists have been surveying GOM seagrass community constituents for at least a decade, and this has allowed us to respond to these natural stressors in an interdisciplinary and holistic manner [Click to see poster]. Monthly sampling was initiated within 10 days of Katrina's landfall at 10 sites along the MS coast. Through a series of bioassay and analytical chemistry measurements of site sediment and water contaminants temporal and special trends of hurricane and oil spill effects are being determined. The Deep Horizon oil spill (2010) represents the greatest anthropogenic disturbance in US territorial waters, and has the potential to severely impact the delicate balance of life along the GOM coastline. Using novel approaches (e.g., proteomic profiling and remote sensing technologies) ETRP scientists continue to address stressors in seagrass and oysters, environmental health, and remediation for the future of the GOM, coastal marine communties, and the citizens of Mississippi who depend on these resources for their livelihood.

  • Carcinogenic, endocrine disruptive and developmental effects of polycyclic aromatic hydrocarbon exposure.
PAHs are ubiquitous environmental contaminants that have been long recognized as carcinogens but more recently are being recognized for the reproductive and developmental toxicities. We use fish as model organisms because they are particularly well suited for study of developmental and multi or transgenerational toxicities. Ongoing work is investigating the potential for benzo(a)pyrene to cause toxicity through epigenetic mechanisms.

  • Fish embryo and gill toxicity of manufactured silver nanoparticles.
The nanoparticle industry is booming, and silver nanoparticles specifically have the highest number of new uses compared to any other. Unfortunately, the toxicological implications of the environmental release of these particles is largely unknown and no regulatory framework exists for them. Our studies will not only highlight mechanisms of toxicity but provide useful information for setting risk guidelines.

  • Coral and sponge disease.
In the marine environment, epidemic outbreaks of unknown diseases have been reported with alarming frequency over the last two decades, yet little is known regarding the causes of these diseases or their effects on hosts, host populations, and communities.  We are studying emerging diseases of coral reef organisms, particularly corals and sponges, and investigating their increased prevalence against the backdrop of natural and anthropogenic stressors, including climate change and nutrient stress.  Combining field and laboratory approaches, we are characterizing the etiology (causes) and pathogenesis (effects) of marine diseases at the individual, population and community levels.  In addition, we are investigating the effects of other environmental stressors on host susceptibility and pathogen virulence, and the role of variability in host immune resistance to disease.

  • Endocrine Disruption in Populations of Sea Urchins and Fish.

Environmental toxins can have significant impacts on the health of individuals. However, the mechanism of action for "endocrine disrupting compounds" is manifested at the population-level. Specifically these compounds block important hormones, thereby causing reproductive impairment, and consequently reduced recruitment into populations. ETRP scientists have been examining PAHs, sewage and paper mill effluents within the GOM to address the cause of sea urchin spawning asynchrony. In the coral reefs of the Bahamas, they have addressed the influence of PAHs and birth control pills, alone and in mixtures, on chemical communication between gobies. In both systems, normal hormone and/or pheromone activities are being impacted by the release of anthropogenic EDCs, and this is having profound implications to population numbers and community health.

  • Ocean Acidification.
The global decline of coral reefs has been attributed to a variety of natural and anthropogenic stressors. However, the consequences of climate change to coral reefs appear to be more dire, longer-term, and potentially irreparable. In particular, the effect of ocean acidification (a result of increased atmospheric CO2, from fossil fuel combustion, dissolving within the oceans on calcification processes may be the most serious threat facing coral reef ecosystems in the coming decades. The increased concentration of CO2 in surface seawater has resulted in a drop of 0.1 pH units, as well as a decline in carbonate ions, that has made it more difficult for marine organisms to either calcify or build aragonite or calcite shells. In addition, elevated CO2 can cause significant effects on physiological functions other than calcification, and increase sensitivity to other stressors. Thus, acidification is likely to change coral reef ecosystems in varied and unpredictable ways, and there is concern that it might trigger the next coral mass extinction. ETRP scientists are currently addressing ocean acidification issues in situ using state-of-the-art techniques, and examining resistance mechanisms that might lead to unique remediation strategies.

Community Health

In addition to working with environmental stress responses, ETRP scientists are also applying their results to issues of environmental and community health. Specifically, novel assays are being used to detect dangerous levels of contaminants in the environment, and specific natural products and enzymes are being used to lower risks of disease.

  • Alcohol use disorders: involvement of alcohol metabolizing enzyme genes.
One of the most common public health problems in the United States is the disorders associated with alcohol drinking. Our approach to the problem is associated with the identification and characterization of specific genes involved in fetal alcohol syndrome (FAS), a lifelong completely preventable set of physical, mental and neurobehavioral birth defects associated with maternal alcohol consumption during pregnancy. Japanese medaka (Oryzias latipes) embryos serve as models in this research. Success has been achieved in characterizing several alcohol metabolizing enzyme genes in this fish and identified aldehyde dehydrogenase (ALDH) is the primary gene whose expression is attenuated by alcohol. We are also screening drugs suitable in the treatment and prevention of FAS in humans, and have initiated screening with natural compounds like vitamins /natural products.

  • Use of in vitro bioassay to assess environmental health.
In vitro tests are being increasingly used as screening tools in risk assessments. In vitro bioassays have several advantages over in vivo approaches for environmental monitoring. Typically they offer a cheaper and more rapid way to screen large numbers of samples with high statistical power for ability to cause a biological response indicative of a particular mechanism of action. We use the H4IIE rat hepatoma bioassay to screen for CYP1A-mediated EROD induction by sediment extracts, and the yeast estrogen screen (YES assay) to assess potential of environmental samples to activate the human estrogen receptor. We have used these methods to screen samples from Mobile Bay, the Miami Canal and Biscayne Bay Florida, and most recently to track coastal recovery following hurricane Katrina.

  • Influence of chirality on biological activity.
Sulfoxidation of thioether-containing organophosphate (OP) insecticides significantly enhances the potency of cholinesterase inhibition. Earlier reports have demonstrated that recombinant flavin-containing monooxygenase 1 (FMO1) catalyzes the oxidation of the OP pesticide fenthion to (+)-fenthion sulfoxide in a stereoselective fashion. In order to elucidate the absolute configuration of the sulfoxide metabolite produced, we established an efficient synthesis of both enantiomers of fenthion sulfoxide (2), which were subsequently transformed to chiral fenoxon sulfoxides (4) using a two-step protocol. The use of chiral oxidants, namely, N-(phenylsulfonyl)(3,3-dichlorocamphoryl) oxaziridines, afforded enantioenriched fenthion sulfoxides with high ee (> 82%) from the parent sulfide. Single recrystallizations afforded chiral fenthion sulfoxides with > 99% ee, measured by chiral HPLC analysis. The absolute configuration of the (+)-sulfoxide generated from fenthion metabolism by FMO1 was determined to be (R)-(+)-fenthion sulfoxide, confirmed by X-ray crystallographic analysis. Evaluation of the inhibition of purified eel acetylcholinesterase (AChE) by fenthion and the individual fenthion and fenoxon sulfoxide enantiomers revealed stereoselective inhibition by R-(+)-fenoxon sulfoxide. Although the enantiomers of fenthion sulfoxide also inhibited AChE more than parent fenthion and fenoxon, no stereoselective effects were observed. Consequently, FMO1 may not only activate fenthion through sulfoxidation to a more toxic metabolite, but subsequent oxidative desulfuration may lead to (R)-(+)- fenoxon sulfoxide formation and further bioactivation.