The effects of acute infection and inflammation on phase II detoxifying enzymes

dc.contributor.author Welch, Darcy L. en_US
dc.date.accessioned 2011-07-22T00:05:08Z
dc.date.available 2011-07-22T00:05:08Z
dc.date.issued 2007 en_US
dc.description Thesis (M.S.)--University of Hawaii at Manoa, 2007. en_US
dc.description Includes bibliographical references (leaves 71-82). en_US
dc.description xiii, 82 leaves, bound 29 cm en_US
dc.description.abstract Infection and inflammation may alter liver metabolism causing significant changes in drug efficacy and toxicity. The expression and activity of the Cytochromes P450 in human liver are significantly down-regulated during acute infection and inflammation but little is known about Phase II metabolizing enzymes. We treated the human liver cell line HepG2 with TNF-α and IL-1β to at 0.1-1000 U/mL for 0-48 hours as a model of acute infection and inflammation. Cells were harvested at each time point and assessed for cell death (MIT assay) and levels of reactive oxygen species (ROS) and for the expression and activity of the major Phase II enzymes UDP-glucuronosyl transferase (UGT), Glutathione-S-transferase (GST) and Sulfotransferase (SULT). Since all of these enzymes have hepatic nuclear factor (HNF) recognition sequences in their genes, we assessed the effects of the cyrokines on HNF1 and HNF4 expression and nuclear translocation with immunofluorescence. UGT enzymes are not significantly affected by pro-inflammatory cytokines and SULT enzymes showed no change in activity while GST enzymes showed a significant increase in activity but returned to norma1levels by 48 hours. Higher GST activity may confer lower efficacy of drugs during acute infection and inflammation. en_US
dc.identifier.uri http://hdl.handle.net/10125/20719
dc.language.iso en-US en_US
dc.relation Theses for the degree of Master of Science (University of Hawaii at Manoa). Microbiology; no. 4262 en_US
dc.rights All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner. en_US
dc.title The effects of acute infection and inflammation on phase II detoxifying enzymes en_US
dc.type Thesis en_US
dc.type.dcmi Text en_US
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