Date on Master's Thesis/Doctoral Dissertation

5-2014

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Cave, Matthew C.

Subject

Liver--Diseases; Pesticides--Toxicology; Pesticides--Health aspects

Abstract

NAFLD, the most common form of liver disease worldwide, is caused by various factors including industrial chemicals and pesticides exposure. Annually, 5.2 billion pounds of pesticides are used worldwide and can contribute to liver disease, but their role is modestly studied. We hypothesize that pesticides contaminating food supply can worsen diet-induced steatosis via xenobiotic receptor activation. Two human and two rodent databases were utilized and 85% of the 330 chemicals identified associated with NAFLD were pesticides. Eight were selected for evaluating hepatic receptor activation in vitro. The majority including DDT activated hPXR/CAR and mPXR. DDT (100 mg/kg) was studied in vivo in a diet-induced obesity (DIO) model. DDT upregulated Cyp2b10 (CAR target) in control diet-fed mice. DDT decreased adiposity, but it did not affect weight gain, food consumption or insulin resistance. In conclusion, DDT improved steatosis, but it did not affect NAFLD, obesity, liver damage or diabetes caused by DIO.

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