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Assessment of acetaminophen-glutathione conjugate toxicity in isolated mitochondria.
Autoři: Roušar Tomáš | Staňková Pavla | Česla Petr | Kučera Otto | Nýdlová Erika | Červinková Zuzana
Rok: 2011
Druh publikace: ostatní - článek ve sborníku
Název zdroje: Twenty years of in Vitro Toxicology: Achievements and Future Challenges
Název nakladatele: ISTISAN Congressi
Místo vydání: Rome
Strana od-do: 90
Tituly:
Jazyk Název Abstrakt Klíčová slova
eng Assessment of acetaminophen-glutathione conjugate toxicity in isolated mitochondria. Introduction: Acetaminophen has been widely used as an analgesic and antipyretic drug. After overdose, it may cause centrilobular liver necrosis and acute liver failure; however, the particular causation of the cell death remains unknown. However, the mail goal of our study was to estimate the possible toxic effect on isolated mitochondria. Methods: To test purified by HPLC technique and confirmed the purity (> 99 %) and structure by HPLC/MS. We assessed rate of respiration (high resolution respirometry, Oroboros 2K, Austria) at complex I and II. Results: We prepared pure APAP-SG conjugate that was used to evaluation of its toxicity. We proved that APAP-SG is able to cause mitochondrial impairment shortly after exposure. In the presence of 2 mM APAP-SG, the respiration was reduced to 43 % and 20 % in Complex I and II, respectively, in both rat and mice mitochondria. Conclusion: We proved our hypothesis that acetaminophen-glutathione conjugate is able to induce mitochondrial impairment.