Vinyl chloride-diet interactions in liver disease : potential roles of autophagy and energy management.

liver disease;vinyl chloride;autophagy;mTOR

Anna L. Lang

University:University of Louisville

Department:Pharmacology and Toxicology

关键词: liver disease;    vinyl chloride;    autophagy;    mTOR;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=3554&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

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.