Project Title: Xenobiotic-Nutrient Interactions for Prevention Against Environmental Chemical Toxicity and Associated Diseases
Principal Investigator: Igor Shmarakov, PhD, Associate Research Scientist, Department of Medicine, Preventive Medicine and Nutrition
Co-Investigator: William S. Blaner, PhD, Professor of Nutritional Medicine, Dept. of Medicine
Award Amount: $35,000
Abstract: Exposure to environmental pollutants contributes to compromised health and the pathology of many age-related diseases, including cancer, diabetes and cardiovascular disease. Effective strategies that mitigate the effects of toxicants on disease etiology and progression are of great public health significance. Our preliminary studies establish that retinoids (vitamin A and its derivatives) directly modulate xenobiotic detoxification and the extent of xenobiotic toxicity in the liver. This pilot project will explore the molecular interactions between polychlorinated biphenyls (PCBs) and retinoids that affect PCB detoxification. PCBs represent the most ubiquitous environmentally persistent organic pollutants, causing liver, kidney, endocrine, and neurodevelopmental toxicities. We will undertake a systematic analysis of how PCB detoxification and toxicity are influenced by retinoid. These studies will employ mutant mouse models lacking key receptor proteins controlling xenobiotic detoxification: constitutive androstane receptor (CAR), pregnane X receptor (PXR) and nuclear factor erythroid 2-related factor 2 (NRF2). Our research will identify key targets of CAR, PXR or NRF2 signaling that are modulated by retinoids. Data generated from the study will support a planned NIH R01 application to more extensively investigate PCB toxicity and how retinoids influence PCB detoxification.