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Characterization of glutathione metabolism in murine liver after acetaminophen treatment.
Autoři: Roušar Tomáš | Roušarová Erika | Česla Petr | Kučera Otto | Červinková Zuzana
Rok: 2015
Druh publikace: ostatní - přednáška nebo poster
Strana od-do: nestránkováno
Tituly:
Jazyk Název Abstrakt Klíčová slova
eng Characterization of glutathione metabolism in murine liver after acetaminophen treatment. Acetaminophen is one of the mostly used antipyretics and analgesics. It is a safe drug at therapeutic doses. However, the overdose can lead to hepatotoxicity followed by liver failure. The cause of cell impairment has been recognized in activation of acetaminophen (APAP) to an oxidized and glutathione-conjugated compound. This compound has been considered as a detoxification product generally. On the other hand, some studies showed that glutathione conjugates may exert also their effects in toxicity. Therefore, the topical aim of our study was to characterize APAP metabolism in murine liver and kidney after APAP overdose. We used c57bl/6 male mice that were treated with acetaminophen (dose 400 mg/g) for 1-48 hours. We measured APAP, APAP-conjugate and glutathione levels in the liver and kidney using LC/MS/MS method. We proved that APAP overdose causes time-related glutathione depletion: after 1 hour, the glutathione level was 1.5 mM and 7 mM in APAP-treated and control mice, respectively. The depletion was mostly produced through formation of APAP-conjugate which levels were near 4 mM after 1h.