Purified Acetaminophen-Glutathione Conjugate Is Able To Induce Oxidative Stress in Rat Liver Mitochondria

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F12%3A39894632" target="_blank" >RIV/00216275:25310/12:39894632 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11150/12:10124777

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Purified Acetaminophen-Glutathione Conjugate Is Able To Induce Oxidative Stress in Rat Liver Mitochondria

Popis výsledku v původním jazyce

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. Weassessed 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 c

Název v anglickém jazyce

Purified Acetaminophen-Glutathione Conjugate Is Able To Induce Oxidative Stress in Rat Liver Mitochondria

Popis výsledku anglicky

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. Weassessed 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 c

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

ED - Fyziologie

OECD FORD obor

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Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2012

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological Reasearch

ISSN

0862-8408

e-ISSN

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Svazek periodika

61

Číslo periodika v rámci svazku

Suppl. 2

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

7

Strana od-do

"S103"-"S109"

Kód UT WoS článku

000310260000012

EID výsledku v databázi Scopus

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