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Study of acetaminophen hepatotoxicity – the toxic effect of acetaminophen-glutathione conjugate on mitochondrial respiration.
Authors: Roušar Tomáš | Staňková Pavla | Pařík Patrik | Kučera Otto | Žáková Pavla | Červinková Zuzana
Year: 2010
Type of publication: ostatní - přednáška nebo poster
Name of source: Česká a slovenská gastroenterologie a hepatologie
Publisher name: Česká lékařská společnost J. E. Purkyně
Place: Praha
Page from-to: S27
Titles:
Language Name Abstract Keywords
eng Study of acetaminophen hepatotoxicity – the toxic effect of acetaminophen-glutathione conjugate on mitochondrial respiration. Currently, we reported that APAP-SG is able to inhibit glutathione reductase, an enzyme that accounts for backward reduction of glutathione disulphide. In the present work, we aimed to follow these results so that we estimated an influence of specific acetaminophen metabolite, APAP-SG on mitochondrial respiration and ROS production. We found that APAP-SG conjugate possessed an inhibition effect on mitochondrial respiration in both complex I and II. APAP-SG (5 mM) decreased the rate of respiration to 26 % and 55 % in complex I and II, respectively. An inhibition effect on complex I activity was found even in 0.2 mM APAP-SG (to 57 % of control signal); however, the complex II activity was not decreased at 0.2 mM APAP-SG. To estimate the level of intramitochondrial ROS production we used DCFDA probe. We proved that ROS formation was enhanced in the presence of APAP-SG and succinate as a substrate: to 900 % and 350 % of control signal, in 5 mM and 1 mM APAP-SG, respectively. acetaminophen; hepatotoxicity; mitochondrial; respiration; glutathione