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Statements

Subject Item
n2:RIV%2F00216208%3A11310%2F14%3A10282870%21RIV15-MSM-11310___
rdf:type
skos:Concept n19:Vysledek
rdfs:seeAlso
http://dx.doi.org/10.1016/j.mrgentox.2014.01.012
dcterms:description
Aristolochic acid is the cause of aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN) and their associated urothelial malignancies. Using Western blotting, we investigated the expression of NAD(P)H:quinone oxidoreductase (NQO1), the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI) in mice and rats. In addition, the effect of AAI on the expression of the NQO1 protein and its enzymatic activity in these experimental animal models was examined. We found that NQO1 protein levels in cytosolic fractions isolated from liver, kidney and lung of mice differed from those expressed in these organs of rats. In mice, the highest levels of NQO1 protein and NQO1 activity were found in the kidney, followed by lung and liver. In contrast, the NQO1 protein levels and enzyme activity were lowest in rat-kidney cytosol, whereas the highest amounts of NQO1 protein and activity were found in lung cytosols, followed by those of liver. NQO1 protein and enzyme activity were induced in liver and kidney of AAI-pretreated mice compared with those of untreated mice. NQO1 protein and enzyme activity were also induced in rat kidney by AAI. Furthermore, the increase in hepatic and renal NQO1 enzyme activity was associated with AAI bioactivation and elevated AAI-DNA adduct levels were found in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, our results indicate that AAI can increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential. Aristolochic acid is the cause of aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN) and their associated urothelial malignancies. Using Western blotting, we investigated the expression of NAD(P)H:quinone oxidoreductase (NQO1), the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI) in mice and rats. In addition, the effect of AAI on the expression of the NQO1 protein and its enzymatic activity in these experimental animal models was examined. We found that NQO1 protein levels in cytosolic fractions isolated from liver, kidney and lung of mice differed from those expressed in these organs of rats. In mice, the highest levels of NQO1 protein and NQO1 activity were found in the kidney, followed by lung and liver. In contrast, the NQO1 protein levels and enzyme activity were lowest in rat-kidney cytosol, whereas the highest amounts of NQO1 protein and activity were found in lung cytosols, followed by those of liver. NQO1 protein and enzyme activity were induced in liver and kidney of AAI-pretreated mice compared with those of untreated mice. NQO1 protein and enzyme activity were also induced in rat kidney by AAI. Furthermore, the increase in hepatic and renal NQO1 enzyme activity was associated with AAI bioactivation and elevated AAI-DNA adduct levels were found in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, our results indicate that AAI can increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential.
dcterms:title
The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study
skos:prefLabel
The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-A comparative study
skos:notation
RIV/00216208:11310/14:10282870!RIV15-MSM-11310___
n3:aktivita
n20:S n20:P n20:I
n3:aktivity
I, P(GA303/09/0472), S
n3:cisloPeriodika
JUL 1 2014
n3:dodaniDat
n10:2015
n3:domaciTvurceVysledku
n13:8486573 n13:6491758 n13:6282555
n3:druhVysledku
n15:J
n3:duvernostUdaju
n14:S
n3:entitaPredkladatele
n7:predkladatel
n3:idSjednocenehoVysledku
13128
n3:idVysledku
RIV/00216208:11310/14:10282870
n3:jazykVysledku
n5:eng
n3:klicovaSlova
DNA adducts; Metabolic activation; Protein expression; NAD(P):quinone oxidoreductase; Aristolochic acid nephropathy
n3:klicoveSlovo
n4:Aristolochic%20acid%20nephropathy n4:Metabolic%20activation n4:DNA%20adducts n4:NAD%28P%29%3Aquinone%20oxidoreductase n4:Protein%20expression
n3:kodStatuVydavatele
NL - Nizozemsko
n3:kontrolniKodProRIV
[00E8090CB4E6]
n3:nazevZdroje
Mutation Research - Genetic Toxicology and Environmental Mutagenesis
n3:obor
n16:CE
n3:pocetDomacichTvurcuVysledku
3
n3:pocetTvurcuVysledku
6
n3:projekt
n8:GA303%2F09%2F0472
n3:rokUplatneniVysledku
n10:2014
n3:svazekPeriodika
768
n3:tvurceVysledku
Bárta, František Arlt, Volker M. Levová, Kateřina Schmeiser, Heinz H. Stiborová, Marie Frei, Eva
n3:wos
000337883400001
s:issn
1383-5718
s:numberOfPages
7
n17:doi
10.1016/j.mrgentox.2014.01.012
n18:organizacniJednotka
11310