Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Committee Co-Chair (if applicable)
liver disease; vinyl chloride; autophagy; mTOR
Vinyl chloride (VC) is a prevalent environmental toxicant that has been shown to cause liver injury at high, occupational exposures. However, most studies have not addressed interactions of low doses with risk-modifying factors. This study aims to explore low-level VC metabolite exposure interactions with other potential risk-modifying factors and their effect on underlying liver disease. We examined sub-hepatotoxic effects of a VC metabolite (chloroethanol, CE) in two murine models of liver injury using ethanol and lipopolysaccharide (LPS). In both, CE significantly enhanced liver injury when compared to either ethanol or LPS alone. Previous studies have shown an increase in mTOR activity with CE alone. Here, we used a pharmacologic inhibitor of mTOR, rapamycin, to study its effect on injury progression. Indeed, the addition of rapamycin significantly attenuated liver injury, hepatic steatosis, and inflammatory markers in the CE + LPS model.
Lang, Anna L., "Vinyl chloride-diet interactions in liver disease : potential roles of autophagy and energy management." (2016). Electronic Theses and Dissertations. Paper 2529.