The UK Superfund Research Center Nutrition and Superfund Chemical Toxicity Director: Bernhard Hennig, Ph.D., R.D. Associate Director: Lindell Ormsbee, Ph.D., P .E. Trainee Presenters: Michael Petriello, Ph.D. Angela Gutiérrez NIEHS Grant: P42ES007380 Center Director (bhennig@uky.edu) www.uky.edu/Research/Superfund/ Program Administrator (j.moore2@uky.edu)
Outline Our Center’s Approach to Mitigating Environmental Health Risks Bernhard Hennig, Ph.D., R.D. (Director) Quantifying Health Risk and Improving Health for Exposed Populations Michael Petriello, Ph.D. (Trainee) Reducing Exposures Through Sensing and Remediation; Translating Findings and Engaging Stakeholders Angela Gutiérrez (Trainee) Superfund Research Center
Contaminants of Interest: PCBs and TCE TCE PCB Sci Total Environ. 2009 Dec 1;407(24):6109-6119 http://img.tarad.com Trichloroethylene (TCE) Polychlorinated biphenyls (PCBs) • Central nervous system and • Inflammation and diabetes endocrine disruptor, carcinogen inducer, carcinogen, endocrine disruptor Superfund Background Research Center
Kentucky Superfund Sites PCBs and TCE prevalent at KY Superfund Sites Federal Superfund Site Federal National Priority List (NPL) Sites * A.L. Taylor (Valley of the Drums) * Howe Valley Landfill 1 11 * Airco Lee’s Lane Landfill 2 12 B.F. Goodrich Maxey Flats Nuclear Disposal 3 13 Brantley Landfill National Electric Coil/Cooper Industries 4 14 Caldwell Lace Leather Co. National Southwire Aluminum Co. 5 15 Distler Brickyard Newport Dump * 6 16 Distler Farm U.S. DOE Gaseous Diffusion Plant 7 17 * Fort Hartford Coal Co. Stone Quarry Red Penn Sanitation Co. Landfill 8 18 General Tire and Rubber (Mayfield Landfill) * Smith’s Farm 9 19 Green River Disposal Tri-City Disposal Co. 10 20 * Sites that are no longer active on the National Priority List Superfund Background Research Center
Paducah Gaseous Diffusion Plant Kentucky’s Largest Superfund Site: TCE, PCBs, Technetium, Heavy Metals, Uranium Superfund Background Research Center
Health Issues in Kentucky Adult obesity rate in Kentucky (1990-2013) High school student obesity rates (2003-2013) 1 st in US 5 th in US Historical adult diabetes rates (1990-2013) Historical adult hypertension rates (1990-2013) 17 th in US 5 th in US 17 th in US The state of obesity – RWJF (2014) Superfund Background Research Center
Possible Therapeutic Interventions 1) Prevent or reduce oxidative stress and inflammation 2) Decrease or prevent body burden (i.e., prevent obesity) 3) Choose a healthy lifestyle, including healthful nutrition, regular exercise, etc. Superfund Background Research Center
Chlorinated Organic Risk Reduction Using Nutrition and Green Chemistry Environmental Exposure and Toxicity to POPs Pollutant Decreased Inflammation Capture Protection NUTRITION Pollutant Against POP Sensing Toxicity Pollutant Antioxidant Effects Degradation Decreased Health Risk Superfund Background Research Center
Outline Our Center’s Approach to Mitigating Environmental Health Risks Bernhard Hennig, Ph.D., R.D. (Director) Quantifying Health Risk and Improving Health for Exposed Populations Michael Petriello, Ph.D. (Trainee) Reducing Exposures Through Sensing and Remediation; Translating Findings and Engaging Stakeholders Angela Gutiérrez (Trainee) Superfund Research Center
Improving Health for Exposed Populations Bernhard Hennig Lisa Cassis Kevin Pearson Hollie Swanson Andrew Morris Arnold Stromberg Superfund Research Center
Quantifying Health Risk Andrew Morris, Ph.D. (a.j.morris@uky.edu) Arnold Stromberg, Ph.D. (astro11@uky.edu) � Analytical Staff: Sony Soman, Ph.D.; Manjula Sunkara, M.S. Statistics Staff: Joshua Lambert, M.S.; Li Xu, M.S. • Analytical support for biomedical and environmental science projects: o Targeted quantitation of PCBs, metabolites and remediation products o Quantitation of bioactive diet-derived mediators and metabolites o Profiling and quantitation of PCBs and related environmental pollutants in clinical and environmental samples • Bio-statistical services provided: o Experimental design o Data analysis o Big data archiving and sharing Superfund Quantifying Health Risk Research Center
Quantifying Health Risk Nutrition Environmental exposure Increased disease risk Trimethylamine N-Oxide: Choline/carnitine metabolite, pro- atherogenic mediator, biomarker • Digestion Polyunsaturated fatty acid: • Endogenous metabolites of healthy fats and metabolism oils, protective mediators • Microbiome metabolism Alkyl resorcinols: Biomarkers of healthy grains Carotenoids and Polyphenols: Biomarkers of fruits and vegetables, protective antioxidants Heritable Factors Protection from risk Methods: HPLC APCI MS/MS, GC MS ECD, GC MS/MS ECD Superfund Quantifying Health Risk Research Center
Quantifying Health Risk Statistical analysis of microarray data and experimental design • consultation The importance of experimental design in mixture analysis • “Big Data” Analysis (e.g., microarray data) • Statistical modeling of PCB mixtures • Analytical and bio-statistical trainee workshops • Superfund Quantifying Health Risk Research Center
Nutrition and Cardiovascular Disease Bernhard Hennig, Ph.D. (bhennig@uky.edu) Andrew Morris, Ph.D. (a.j.morris@uky.edu) Post Doc Trainees: Mike Petriello, Ph.D.; Banrida Wahlang, Ph.D. Graduate Trainees: Jordan Perkins, Jessie Hoffman Overall goal: Utilize healthful nutrition as a sensible means of decreasing cardiovascular disease risks associated with environmental pollutants. Superfund Improved Health for Exposed Populations Research Center
Background and Significance A growing and convincing body of research indicates that nutrition may function as a modulator of vulnerability to environmental insults with nutrition serving to both better or worsen the health impacts associated with exposure to environmental toxins. Cl Cl Cl Cl Cl Kentucky has Exposure high incidence of Cardiovascular obesity, diabetes, diseases Diabetes cardiovascular disease, poverty, Obesity Cancer and poor nutrition Suppression of Oxidative Dysfunction of the immune system damage reproductive and nervous systems http://www.epa.gov/opptintr/pcb/ Superfund Improved Health for Exposed Populations Research Center
Ongoing Research 12.0 5.0 • Utilize in vitro and in vivo GSTm3 mRNA level (Fold change) * NQO1 mRNA level (Fold change) 4.5 * 10.0 molecular biology 4.0 3.5 8.0 techniques and knock-out 3.0 * 6.0 2.5 animal models to determine 2.0 4.0 1.5 signaling pathways critical to 1.0 2.0 PCB-induced 0.5 0.0 0.0 Vehicle PCB 126 Vehicle PCB 126 atherosclerosis and 1.2 1.8 Liver mRNA levels of multiple antioxidant ) ) nutritional modulation. enzymes were upregulated in mice fed GTE and exposed to PCB Superfund Improved Health for Exposed Populations Research Center
Take Home Message Exposure to PCBs and other pollutants may lead to chronic inflammation and heart disease, but eating diets high in antioxidant and anti-inflammatory bioactive nutrients such as those found in fruits and vegetables may buffer the body against toxic insult. Superfund Improved Health for Exposed Populations Research Center
Postnatal Complications of Perinatal Exposures Kevin Pearson, Ph.D. (kevin.pearson@uky.edu) Hollie Swanson, Ph.D. (hswan@email.uky.edu) Post Doc Trainee: Leryn Reynolds, Ph.D. Overall goal: Contribute new Developmental origins of health and disease insights to understand the potential long-term health complications of PCB toxicity during critical periods of in utero PCB exposure Maternal exercise and early postnatal life and explore ??? ??? e Increase s a the role of maternal exercise as a ??? e ??? r c e D transgenerational intervention. OFFSPRING Obesity Diabetes Superfund Improved Health for Exposed Populations Research Center
Background and Significance • PCBs can cross the placenta and enter into breast milk (levels of pollutants may be >5 times higher in milk than in maternal blood). • Recent studies indicate that prenatal exposures to polychlorinated biphenyls (PCBs) contribute to gender- specific obesity development in children. Superfund Improved Health for Exposed Populations Research Center
Ongoing Research PCB Maternal Inflammation Glucose Intolerance Fetal Programming Offspring Obesity and Glucose Intolerance Superfund Improved Health for Exposed Populations Research Center
Ongoing Research PCB Maternal Inflammation Placenta Glucose Intolerance PCB Fetal Programming Offspring Obesity and Glucose Intolerance Superfund Improved Health for Exposed Populations Research Center
Ongoing Research PCB Maternal Inflammation Placenta Glucose Intolerance Breast Milk PCB Fetal Programming PCB Offspring Obesity and Glucose Intolerance Superfund Improved Health for Exposed Populations Research Center
Maternal PCB 126 Exposure Alters Offspring Body Composition and Glucose Tolerance Wean Offspring blood glucose (mg/dL) ** * 500 Day -28 -21 -14 -7 0 7 14 21 mating 400 gestation 300 200 100 Control PCB 0 0 20 40 60 80 100 120 Time (min) Pups born to mothers treated with PCBs exhibit glucose intolerance and inflammation Carter et. al. Am J Physiol Endocrinol Metab 2012 Rashid et. al. J Ped Biochem 2013 Superfund Improved Health for Exposed Populations Research Center
Recommend
More recommend
