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Evaluation of glutathione metabolism in cultured rat hepatocytes during acetaminophen injury.
Authors: Roušar Tomáš | Kučera Otto | Křiváková Pavla | Lotková Halka | Mužáková Vladimíra | Červinková Zuzana
Year: 2007
Type of publication: článek ve sborníku
Name of source: Free Radical Research
Publisher name: Informa Healthcare UK
Place: London
Page from-to: 51-52
Titles:
Language Name Abstract Keywords
cze Monitorování metabolismu glutathionu v kultivovaných hepatocytech během toxického působení acetaminofenu Monitorování metabolismu glutathionu v kultivovaných hepatocytech během toxického působení acetaminofenu
eng Evaluation of glutathione metabolism in cultured rat hepatocytes during acetaminophen injury. Acetaminophen (AAP) is a safe analgesic and antipyretic drug when used at therapeutic doses. On the other hand, the AAP overdose is one of the most frequent causes of drug-induced acute liver failure. Albeit the mechanisms of AAP injury have been extensively studied recently, some of them remain to resolve. Glutathione is an essential compound acting in detoxification of AAP because it binds to the active metabolite, N-acetyl-p-benzoquinone imine (NAPQI). After depletion of GSH levels, NAPQI binds to number of cellular proteins. The aim of our study was to evaluate the changes in glutathione metabolism, GSH and GSSG levels and glutathione reductase (GR) activity, during AAP injury. Especially, we focused on time course of changes with respect to increasing AAP doses. Hepatocytes were isolated from male Wistar rats by collagenase perfusion and cultivated on collagen-coated 24-well plates. Our results proved that the activity of GR is evidently decreased in relation to AAP concentration and time of incubation (after 24 h incubation with AAP 5 mM, 10 mM and 20 mM, respectively ? activity of GR compared to controls: 60+/-6%, 36+/-5% and 21+/-7%, respectively). Acetaminophen; oxidative stress; hepatocyte