Superfund Research Program

Biomonitoring and Environmental Analytical Chemistry Core

Project Leader: Angela M. Gutierrez
Grant Number: P42ES007380
Funding Period: 2005-2025

Project-Specific Links

Final Progress Reports

Year:   2019  2013  2007 

Studies and Results

The overarching purpose of the Research Support Core of the University of Kentucky Superfund Research Program Center (UK-SRP Center) is to provide vital access to expertise, research resources and state of the art instrumentation to researchers engaged in all aspects of the component biomedical and environmental science (non-biomedical) research projects. The Research Support Core enhances the productivity, quality and consistency of these component projects by providing a formalized mechanism for access to expert investigators and professional staff and enabling efficient use of expensive and sophisticated instrumentation for routine and specialized purposes that would otherwise be beyond the capabilities of individual laboratories to acquire and support. A major focus of this Core is on the development and implementation of methods using a highly sensitive and specific technique called mass spectrometry to identify and measure environmental toxins, nutritional protectants, and their metabolites with a particular interest in the possibility that these may be mediators of cardiovascular disease, diabetes and complications of obesity including inflammation. This work is accomplished using state of the art instruments with distinct and complementary capabilities. A particular area of emphasis in the past year has been on using their analytical capabilities to assist UK SRC researchers who are engaged in research that seeks to define protective actions of specific dietary constituents against the deleterious effects of Superfund pollutants, e.g., PCBs. Some highlights of this work include:

• Dietary flavonoids have been shown to exert protective effects against toxicity associated with exposure of vascular cells to PCBs in vitro but much less is known about their protective effects in vivo. The Research Support Core developed mass spectrometry methods to measure systemic levels of flavonoids in green tea extracts following oral administration in mice. They also established methods to measure levels of isoprostanes which are oxidized lipid markers of oxidative stress in urine and blood. These methods were used to show that dietary supplementation with green tea extracts significantly attenuates PCB associated increases in these oxidized lipids. PMID: 24378064
• Resveratrol is another plant derived substance that exhibits beneficial effects on some of the metabolic abnormalities such as defective glucose homeostasis that are associated with exposure to PCBs. The Research Support Core used mass spectrometry to measure plasma and tissue levels of PCBs and resveratrol following oral administration in mice. These measurements were an important component of a study that identified a protective effect of resveratrol against PCB induced impairment of glucose homeostasis. PMID: 24231106
• Certain polyunsaturated fatty acids, particularly those found in abundance in fish oil, have been proposed to exert beneficial health effects in several settings, notably cardiovascular disease and the complications of obesity such as diabetes. One idea to explain these effects is that these fatty acids can be converted in the body to substances that are themselves protective. Several compounds formed by enzymatic or non-enzymatic oxidation of these fatty acids have potent ant inflammatory effects in cell culture systems and animal models. To extend this work to humans, the Core established methods to measure these fish oil fatty acids and their active metabolites and used these methods to show that after oral consumption the fatty acids become incorporated into fats in the body. Their study suggested that some kinds of white blood cells that accumulate in tissues during inflammation might mediate the protective effects of these fatty acids by promoting production of these ant inflammatory fatty acid derived mediators. PMID: 23328126
• The Research Support Core has developed methods to measure a series of other diet derived biologically active lipids and used these methods to identify roles for these lipids in several physiological and pathophysiological processes. These include studies of cardiovascular function and disease and the mechanisms that control the mobilization, homing and engraftment of bone marrow derived stem cells and infection. PMID: 23615526 PMID: 23282236 PMID: 23104851 PMID: 24150174 PMID: 23995678 PMID: 23948545
• The Research Support Core also provides capabilities for biostatistics and data sharing. Dr. Stromberg and his RA are available for statistical consultations for all Superfund researchers. Importantly, over half of the trainees have sought out advice. The most extensive collaboration was with trainee Carolyn Hofe and Lisa Gaetke on an NHANES analysis that showed a positive or protective impact of nutrition on high BMI and high PCB exposure with regard to developing type-2 diabetes. Their paper is under revision.

Significance

The overarching goal of the University of Kentucky Superfund Research Program (UK-SRP) Center is to establish strategies for detection and elimination of polychlorinated biphenyls (PCBs) from the environment and to define mechanisms of PCB toxicity responsible for cardiovascular and metabolic diseases in both adults and during pregnancy. A common theme of the UK-SRC is the evaluation of nutrition based strategies for protection against PCB toxicity. As detailed above, the significance of the research conducted by the Core laboratory is that it enables these studies by providing capabilities for structural analysis and quantitation of toxins, nutrients and their metabolites. In the past year, these technologies have been used to make important discoveries about the mechanisms underlying beneficial effects of specific dietary constituents against PCB toxicity and some of the consequences of exposure to PCBs.