Date on Master's Thesis/Doctoral Dissertation

8-2025

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Watson, Walter

Committee Co-Chair (if applicable)

Cave, Matthew

Committee Member

Srivastava, Sanja

Committee Member

Kidd, La Creis

Committee Member

Wahlang, Banrida

Author's Keywords

Alcohol-associated liver disease; PFOS; enviornmental liver disease; nuclear receptors

Abstract

Perfluorooctane sulfonate (PFOS), a pervasive environmental pollutant, has been increasingly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD); nonetheless, its connections with alcohol-associated liver disease (ALD) have not been well studied. This study investigates the hypothesis that PFOS exposure alters hepatic metabolism, thereby leading to alterations in ALD severity. Male C57BL/6J mice were fed isocaloric control or 5% ethanol (EtOH) diet for 15 days. From day 6 of feeding, mice were concurrently gavaged with 1 mg/kg PFOS or 2% Tween-80 vehicle for 10 days, followed by a 5 g/kg EtOH binge dose. PFOS and ethanol co-exposure significantly increased transcription of several notable transcription factors including peroxisome proliferator-activated receptor alpha (PPARα), constitutive androstane receptor (CAR), and pregnane x receptor (PXR). Furthermore, dual-exposure worsened ALD severity by increasing liver injury, steatosis, lipid dysregulation, and by enriching hepatic transcriptional pathways. Overall, these findings suggest that PFOS worsens ALD severity.

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