Item – Theses Canada

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OCLC number
30069369
Author
Rafeiro, Elizabeth,1966-
Title
Mechanisms of glutathione replenishment by N-acetylcysteine and dithiothreitol following acetaminophen-induced toxicity in isolated mouse hepatocytes.
Degree
M. Sc. -- Queen's University, 1992
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, 1993.
Description
2 microfiches.
Notes
University Microfilms order no. UMI00379764.
Includes bibliographical references.
Abstract
Incubation of isolated mouse hepatocytes with 1.0 mM acetaminophen (AA) for 1.5 hr was sufficient to initiate and allow the progression of cytotoxicity during the 4 hr incubation period. Cytotoxicity was assessed by using the lactate dehydrogenase (LDH) latency assay which indicates a loss of plasma membrane integrity. The procedure used to wash AA from hepatocytes was shown to remove the majority of the non-covalently bound AA from hepatocyte suspensions. The mechanism(s) of GSH replenishment by N-acetylcysteine (NAC) and dithiothreitol (DTT) were examined following AA-initiated GSH depletion and toxicity. The results suggest that the mechanisms of GSH replenishment by NAC and DTT are dependent on de novo GSH synthesis. GSH replenishment by NAC in the post-reaction phase was not sufficient to protect against AA-initiated toxicity. GSH replenishment by DTT was accompanied by protection against cytotoxicity. However, the DTT-induced attenuation of cytotoxicity following AA and BSO pretreatment was not dependent on GSH replenishment suggesting that other mechanism(s) account at least in part for DTT's protective function. (Abstract shortened by UMI.)
Subject
Glutathione.
Acetylcysteine.
Dithiothreitol.
Acetaminophen Toxicology.
Buthionine sulfoximine.
Hepatotoxicology.
Liver cells.
Glutathion.
Paracétamol Toxicologie.
Hépatotoxicité.
Cellules hépatiques.
ISBN
0315764643
9780315764644