Date on Master's Thesis/Doctoral Dissertation

12-2021

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Barve, Shirish

Committee Member

McClain, Craig

Committee Member

Ghare, Smita

Committee Member

Gobejishvili, Leila

Committee Member

Hein, David

Author's Keywords

Histone deacetylases; alcohol; Liver; mouse

Abstract

Alcohol abuse is endemic worldwide and there is no FDA approved treatment for Alcohol-Associated Liver Disease (ALD). Many scholars have posited that targeting Histone Deacetylases (HDAC) may be therapeutic in ALD intervention. In this study, the changes in hepatic gene expression and immune phenotyping of mice undergoing chronic plus binge alcohol exposure was examined. The characterization of relative mRNA levels for all 18 HDAC were performed. Results showed decreased expression of the genes HDAC 1,7,9,10,11 and Sirtuin enzymes (SIRT) 3,4,5,7. Other pathways related to lipid metabolism as well as systemic inflammation and hepatic injury also exhibited significant changes. These altered pathways were normalized with the administration of the HDAC inhibitor Trichostatin A (TSA) in primary mouse hepatocytes. These results suggest the potential importance of HDAC dysregulation in ALD mouse models. Future studies should investigate the interactions between HDAC and the molecular mechanisms that control the gut-liver-brain axis.

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