Date of Award

2018

Degree Type

Thesis

Degree Name

Master of Science in Pharmaceutical Sciences

Department

Biomedical and Pharmaceutical Sciences

First Advisor

Fatemeh Akhlaghi

Abstract

Background and Objectives:

Diabetes mellitus and Non-Alcoholic Fatty Liver Disease (NAFLD) are two highly prevalent and related diseases. Research have shown that they can affect the expression and activity of enzymes integral in the clearance of xenobiotics. Such enzymes include the Cytochrome P-450 isoforms 2C8 and 2C9. Our objective is to study the effect of these diseases on CYP2C8 and CYP2C9 using in vitro tools.

Methods:

A bank of donated livers was utilized for in vitro studies. Hepatic microsomal incubations of S-warfarin, a (CYP2C9) probe substrate, were performed to measure CYP2C9 activity by product formation and S-warfarin, intrinsic clearance by in vitro half-life approach. Additionally, previously acquired data in our lab on mRNA and protein levels of CYP2C8 and CYP2C9 have been analyzed and compared among diabetic and NAFLD groups.

Results and Conclusions:

Analysis of CYP2C8 mRNA and protein expression in addition to CYP2C9 mRNA expression, activity, and warfarin’s intrinsic clearance showed no significant alteration by NAFLD nor diabetes. CYP2C9 protein expression significantly varied between different diabetic and NAFLD populations (p = 0.047).

Available for download on Monday, November 30, 2020

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