Metabolic Studies of Hepatic Response to Diabetes Drugs.
Abstract: A major
concern in drug development is the potential for chemical injury to the liver. Drugs
account for 1/3~1/2 of acute liver failures, yet underlying toxicity mechanisms are
poorly understood. Adverse reactions are often detected too late, as with troglitazone,
an antidiabetic drug introduced in 1997 and withdrawn in 2000 after several cases of
liver failure. Predictions are more ... read morelimited with multi-drug interactions, common among
patients with chronic ailments like diabetes. Here we develop a microfluidic reactor for
the culture of HepG2 cells and the establishment of a steady state drug gradient.
Traditional in vitro experiments explore the metabolic effects of troglitazone on HepG2
cells and the interactions between rosiglitazone and metformin (common antidiabetic
compounds). LC-MS methods are developed for the detection of drugs and key metabolites.
This research expands our knowledge drug metabolism in the liver and introduces a
physiologically relevant platform for the testing of drug
Thesis (M.S.)--Tufts University, 2011.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: Kyongbum Lee.
Committee: Daniel Ryder, and Catherine Kuo.
Keyword: Chemical engineering.read less