Date on Master's Thesis/Doctoral Dissertation

8-2016

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Arteel, Juliane

Committee Co-Chair (if applicable)

Arteel, Gavin

Committee Member

Arteel, Gavin

Committee Member

Cave, Matt

Committee Member

Wise, John

Committee Member

Freedman, Jonathan

Committee Member

Prough, Russell

Author's Keywords

liver disease; vinyl chloride; autophagy; mTOR

Abstract

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.

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