Acute and Sub-Chronic Exposures to Dioxin and Dioxin-Like Compounds in Liver Disease: The Role of Sex and Age
Abstract
The overarching objective of the proposed project is to understand how exposures to burn pit chemicals, categorized as persistent organic pollutants (POPs), affect liver health and disease and how factors such as biological sex and age influence these effects. Also known as Forever chemicals, POPs are environmental chemicals that persist in the environment and continue to be detected in human samples representing the American general population. Open pit burning, which was a standard military procedure for waste disposal at military base camps, resulted in massive emissions of toxic chemicals (toxicants) like POPs and others. These emitted POPs included a variety of chemicals including dioxins, polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). Open burning occurred for several decades until recent substituted methods were implemented and affected Service Members deployed to U.S. military bases across the globe. Studies evaluating health hazards cause by exposures to burn pit chemicals have focused primarily on lung and cardiovascular disorders. However, the effects of these burn pit chemical mixtures on other organs such as the liver remains to be elucidated. The liver is a primary target organ for chemical exposures because of its inherent function in the body in breaking down and facilitating the excretion of foreign compounds including drugs, nutrients, and so forth. Liver function and characteristics are also different, based on biological sex. Further, biological sex plays an important role in dictating disease outcomes from toxic exposures due to differences in sex hormone levels among other factors. Biological processes throughout the lifespan are also different in males and females, and confounded by factors including pregnancy, lactation, menstruation, and menopause. Moreover, the effects of toxic exposures can also change with age or time after exposure. Thus, the proposal aims to understand the sex-specific and time-dependent impact of toxic chemical exposures and will utilize preclinical exposure models to carry out the proposed studies. The study goals include obtaining evidence of burn pit chemical toxicities on vital organs such as the liver and their contribution to liver disease; understanding how such toxicities are brought upon or induce and how they differ in males vs. females; and investigating the modifications in the body caused by toxic chemical exposures (e.g., changes in protein levels or gut bacteria) and how they can potentially be used as surrogate identifiers of disease (biomarkers) to better diagnose the disease. The proposed research addresses FY22 TERP Program Goals, namely Elucidating mechanisms of how toxic exposures result in adverse effects and Diagnose the effects of toxic exposures. The proposed research also falls in line with FY22 TERP Topic Areas, namely Airborne hazards and burn pits and its accompanying Focus Area, Identify toxicants associated with airborne hazards and elucidate mechanisms. The interim outcomes from this 3-year basic science research will provide scientific knowledge on the harmful effects of POPs in the liver and how these effects compare in males vs. females. The knowledge obtained will include information on how these chemicals impair the liver from performing its normal function, what is the fate of such toxic effects with time, how does liver disease progress with age, and how do lifestyle factors such as consumption of high-caloric diets influence chemically induced liver disease. The findings will also inform us of how these effects are brough upon and what are the exact proteins and hormones that the chemicals are targeting or modifying. Understanding these mechanisms will help researchers in using such modified protein and hormone landscape as biomarkers or diagnostic tools in exposed human populations. The likely contributions from this proposed research include scientific and biomedical adva
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310949
Entities
People
- Banrida Wahlang
Organizations
- United States Army
- University of Louisville