Purified acetaminophen-glutathione conjugate is able to induce oxidative stress in rat liver mitochondria

Title:

Purified acetaminophen-glutathione conjugate is able to induce oxidative stress in rat liver mitochondria

Creator:

Tomáš Roušar, Nýdlová, E., Petr Česla, Pavla Křiváková, Otto Kučera, Patrik Pařík, and Zuzana Červinková

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:ed197f58-4f36-4622-b3ae-82b478a74a01
uuid:ed197f58-4f36-4622-b3ae-82b478a74a01

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie člověka, human physiology, acetaminophen toxicity, glutathione, acetaminophenglutathione conjugate, 14, and 612

Type:

article, články, model:article, and TEXT

Description:

Acetaminophen overdose is the most often cause of acute liver injury. The toxic mechanism is linked to formation of an active metabolite that reacts with glutathione generating acetaminophen-glutathione conjugate (APAP-SG). This compound has been recognized to be non-toxic generally. Our preliminary results showed, however, that APAP-SG could possess a toxic effect too. Therefore, the aim of our study was to prepare, purify and to test possible toxicity of APAP-SG. We prepared APAP-SG using organic synthesis. The conjugate was purified by preparative HPLC and its structure was confirmed using mass spectrometry. Final purity of APAP-SG was >98 %. We estimated a toxic effect of APAP-SG in isolated rat liver mitochondria using a fluorescent ROS probe. We assessed ROS production in presence of complex I or complex II substrates. The increase of ROS-dependent fluorescence in presence of glutamate/malate was 104±13 % and 130±10 % in 1 mM and 5 mM APAP-SG, respectively, in comparison with controls. ROS production related to presence of complex II substrate was enhanced 4-times in APAP-SG (5 mM) treated mitochondria (compared to controls). We conclude, we proved our hypothesis that APAP-SG conjugate is able to induce a mitochondrial impairment leading to enhanced ROS production., T. Roušar, ... [et al.]., and Obsahuje seznam literatury

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2012 Volume:61 | Number:Suppl 2

Harvested from:

CDK

Metadata only:

false