The influence of dicoumarol on the bioactivation of the carcinogen aristolochic acid I in rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F14%3A10282776" target="_blank" >RIV/00216208:11310/14:10282776 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1093/mutage/geu004" target="_blank" >http://dx.doi.org/10.1093/mutage/geu004</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/mutage/geu004" target="_blank" >10.1093/mutage/geu004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The influence of dicoumarol on the bioactivation of the carcinogen aristolochic acid I in rats

Popis výsledku v původním jazyce

Aristolochic acid I (AAI) is the major toxic component of the plant extract AA, which leads to the development of nephropathy and urothelial cancer in human. Individual susceptibility to AAI-induced disease might reflect variability in enzymes that metabolise AAI. In vitro NAD(P)H:quinone oxidoreductase (NQO1) is the most potent enzyme that activates AAI by catalyzing formation of AAIDNA adducts, which are found in kidneys of patients exposed to AAI. Inhibition of renal NQO1 activity by dicoumarol has been shown in mice. Here, we studied the influence of dicoumarol on metabolic activation of AAI in Wistar rats in vivo. In contrast to previous in vitro findings, dicoumarol did not inhibit AAIDNA adduct formation in rats. Compared with rats treated withAAI alone, 11- and 5.4-fold higher AAIDNA adduct levels were detected in liver and kidney, respectively, of rats pretreated with dicoumarol prior to exposure to AAI. Cytosols and microsomes isolated from liver and kidney of these rats wer

Název v anglickém jazyce

The influence of dicoumarol on the bioactivation of the carcinogen aristolochic acid I in rats

Popis výsledku anglicky

Aristolochic acid I (AAI) is the major toxic component of the plant extract AA, which leads to the development of nephropathy and urothelial cancer in human. Individual susceptibility to AAI-induced disease might reflect variability in enzymes that metabolise AAI. In vitro NAD(P)H:quinone oxidoreductase (NQO1) is the most potent enzyme that activates AAI by catalyzing formation of AAIDNA adducts, which are found in kidneys of patients exposed to AAI. Inhibition of renal NQO1 activity by dicoumarol has been shown in mice. Here, we studied the influence of dicoumarol on metabolic activation of AAI in Wistar rats in vivo. In contrast to previous in vitro findings, dicoumarol did not inhibit AAIDNA adduct formation in rats. Compared with rats treated withAAI alone, 11- and 5.4-fold higher AAIDNA adduct levels were detected in liver and kidney, respectively, of rats pretreated with dicoumarol prior to exposure to AAI. Cytosols and microsomes isolated from liver and kidney of these rats wer

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

<a href="/cs/project/GA303%2F09%2F0472" target="_blank" >GA303/09/0472: Studium participace biotransformačních enzymů na vývoji ledvinného selhání a nádorů močových cest vyvolaných aristolochovou kyselinou</a><br>

Návaznosti

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

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

Mutagenesis

ISSN

0267-8357

e-ISSN

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Svazek periodika

29

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

189-200

Kód UT WoS článku

000334677200004

EID výsledku v databázi Scopus

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